System and method for safety syringe

ABSTRACT

A method for preparing a pre-filled multi-chamber injection system includes providing an injection system body, the injection system body defining an open proximal end, a body interior, and an open distal end. The method also includes introducing a first substance into a distal end of the body interior. The method further includes disposing a distal stopper member in the body interior, the distal stopper member and the injection system body defining proximal and distal chambers in the body interior. Moreover, the method includes introducing a second substance into the body interior. In addition, the method includes disposing a proximal stopper member in the body interior. The method also includes inserting an elongate member at least partially into the body interior, the elongate member having a plurality of flow channels for fluidly coupling the proximal and distal chambers. The method further includes coupling a plunger member to the proximal stopper member.

The present application is a continuation of U.S. patent applicationSer. No. 16/798,188 filed on Feb. 21, 2020 entitled “SYSTEM AND METHODFOR SAFETY SYRINGE”, which claims priority to (1) U.S. ProvisionalPatent Application Ser. No. 62/809,369, filed on Feb. 22, 2019 underattorney docket number CM.30023.00, and entitled “SYSTEM AND METHOD FORSAFETY SYRINGE” and (2) U.S. Provisional Patent Application Ser. No.62/864,509, filed on Jun. 21, 2019 under attorney docket numberCM.30026.00, and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE.” Thisapplication also includes subject matter similar to the subject matterdescribed in the following co-owned U.S. patent applications: (3) U.S.Utility patent application Ser. No. 14/321,706, filed Jul. 1, 2014 underattorney docket number CM.20001.00 and entitled “SAFETY SYRINGE”; (4)U.S. Utility patent application Ser. No. 14/543,787, filed Nov. 17, 2014under attorney docket number CM.20002.00 and entitled “SYSTEM AND METHODFOR DRUG DELIVERY WITH A SAFETY SYRINGE”; (5) U.S. Utility patentapplication Ser. No. 14/696,342, filed Apr. 24, 2015 under attorneydocket number CM.20003.00 and entitled “SYSTEM AND METHOD FOR SAFETYSYRINGE”; (6) U.S. Utility patent application Ser. No. 15/801,239, filedon Nov. 1, 2017 under attorney docket number CM.20011.00 and entitled“SYSTEM AND METHOD FOR SAFETY SYRINGE”; (7) U.S. Utility patentapplication Ser. No. 15/801,259, filed on Nov. 1, 2017 under attorneydocket number CM.20012.00 and entitled “SYSTEM AND METHOD FOR SAFETYSYRINGE”; (8) U.S. Utility patent application Ser. No. 15/801,281 filedon Nov. 1, 2017 under attorney docket number CM.20013.00 and entitled“CARTRIDGE SAFETY INJECTION SYSTEM AND METHODS”; (9) U.S. Utility patentapplication Ser. No. 15/801,304 filed on Nov. 1, 2017 under attorneydocket number CM.20015.00 and entitled “SYSTEM AND METHOD FOR SAFETYSYRINGE”; (10) U.S. Provisional Patent Application Ser. No. 62/682,381filed on Jun. 8, 2018 under attorney docket number CM.30019.00 andentitled “SYSTEM AND METHOD FOR SAFETY SYRINGE”; and (11) U.S.Provisional Patent Application Ser. No. 62/729,880 filed on Sep. 11,2018 under attorney docket number CM.30021.00 and entitled “SYSTEM ANDMETHOD FOR SAFETY SYRINGE.” The contents of the above-mentionedapplications are fully incorporated herein by reference as though setforth in full.

FIELD OF THE INVENTION

The present invention relates generally to injection systems, devices,and processes for facilitating various levels of control over fluidinfusion, and more particularly to systems and methods related tomultiple chamber safety syringes in healthcare environments.

BACKGROUND

Millions of syringes, such as that depicted in FIG. 1A (2), are consumedin healthcare environments every day. A typical syringe (2) comprises atubular body (4), a plunger (6), and an injection needle (8). As shownin FIG. 1B, such a syringe (2) may be utilized not only to inject fluidinto a patient, but also to withdraw or expel fluid out of or into acontainer such as a medicine bottle, vial, bag, or other drugcontainment system (10). Indeed, due to regulatory constraints in somecountries such as the United States as well as sterility maintenanceconcerns, upon use of a medicine bottle (10) with a syringe (2) as shownin a particular patient's environment, such medicine bottle may only beutilized with a single patient and then must be disposed of—causingsignificant medical waste from bottle and remaining medicine disposal,and even contributing to periodic shortages of certain critical drugs.Referring to FIG. 2A, three Luer-type syringes (12) are depicted, eachhaving a Luer fitting geometry (14) disposed distally, so that they maybe coupled with other devices having similar mating geometry, such asthe Luer manifold assembly (16) depicted in FIG. 2B. The Luer manifoldassembly of FIG. 2B may be used to administer liquid drugs to thepatient intravenously with or without the use of an intravenous infusionbag. The Luer fittings (14) of the syringes of FIG. 2A may be termed the“male” Luer fittings, while those of FIG. 2B (18) may be termed the“female” Luer fittings; one of the Luer interfaces may be threaded (inwhich case the configuration may be referred to as a “Luer lock”configuration) so that the two sides may be coupled by relativerotation, which may be combined with compressive loading. In otherwords, in one Luer lock embodiment, rotation, possibly along withcompression, may be utilized to engage threads within the male fitting(14) which are configured to engage a flange on the female fitting (18)and bring the devices together into a fluid-sealed coupling. In anotherembodiment, tapered interfacing geometries may be utilized to providefor a Luer engagement using compression without threads or rotation(such a configuration may be referred to as a “slip-on” or “conical”Luer configuration). While such Luer couplings are perceived to berelatively safe for operators, there is risk of medicinespilling/leaking and parts breakage during assembly of a Luer coupling.The use of needle injection configurations, on the other hand, carrieswith it the risk of a sharp needle contacting or stabbing a person orstructure that is not desired. For this reason, so called “safetysyringes” have been developed.

One embodiment of a safety syringe (20) is shown in FIG. 3 , wherein atubular shield member (22) is spring biased to cover the needle (8) whenreleased from a locked position relative to the syringe body (4).Another embodiment of a safety syringe (24) is shown in FIGS. 4A-4B.With such a configuration, after full insertion of the plunger (6)relative to the syringe body (4), the retractable needle (26) isconfigured to retract (28, 26) back to a safe position within thetubular body (4), as shown in FIG. 4B. Such a configuration which isconfigured to collapse upon itself may be associated with bloodspatter/aerosolization problems, the safe storage of pre-loaded energywhich may possible malfunction and activate before desirable, loss ofaccuracy in giving full-dose injections due to residual dead spacewithin the spring compression volume, and/or loss of retraction velocitycontrol which may be associated with pain and patient anxiety.

Further complicating the syringe marketplace is an increasing demand forprefilled syringe assemblies such as those depicted in FIGS. 5A and 5B,which generally comprise a syringe body, or “drug enclosure containmentdelivery system”, (34), a plunger tip, plug, or stopper (36), and adistal seal or cap (35) which may be fitted over a Luer type interface(FIG. 5A shows the cap 35 in place; FIG. 5B has the cap removed toillustrate the Luer interface 14). Liquid medicine may reside in thevolume, or medicine reservoir, (40) between the distal seal and thedistal end (37) of the plunger tip (36). The plunger tip (36) maycomprise a standard butyl rubber material and may be coated, such aswith a biocompatible lubricious coating (e.g., polytetrafluoroethylene(“PTFE”)), to facilitate preferred sealing and relative motioncharacteristics against the associated syringe body structure andmaterial. The proximal end of the syringe body (34) in FIG. 5B comprisesa conventional integral syringe flange (38), which is formed integral tothe material of the syringe body (34). The flange (38) is configured toextend radially from the syringe body (34) and may be configured to be afull circumference, or a partial circumference around the syringe body(34). A partial flange is known as a “clipped flange” while the other isknown as a “full flange.” The flange is used to grasp the syringe withthe fingers to provide support for pushing on the plunger to give theinjection. The syringe body (34) preferably comprises a translucentmaterial such as a glass or polymer. To form a contained volume withinthe chamber or reservoir (40), and to assist with expulsion of theassociated fluid through the needle, a plunger tip (36) may bepositioned within the syringe body (34). The syringe body (34) maydefine a substantially cylindrical shape (i.e., so that a plunger tip 36having a circular cross-sectional shape may establish a seal against thesyringe body (34)), or be configured to have other cross-sectionalshapes, such as an ellipse.

Such assemblies are desirable because they may be standardized andproduced with precision in volume by the few manufacturers in the worldwho can afford to meet all of the continually changing regulations ofthe world for filling, packaging, and medicine/drug interfacingmaterials selection and component use. Such simple configurations,however, generally will not meet the new world standards for single-use,safety, auto-disabling, and anti-needle-stick. Thus certain suppliershave moved to more “vertical” solutions, such as that (41) featured inFIG. 5C, which attempts to meet all of the standards, or at least aportion thereof, with one solution; as a result of trying to meet thesestandards for many different scenarios, such products may havesignificant limitations (including some of those described above inreference to FIGS. 3-4B) and relatively high inventory and utilizationexpenses.

In some cases, multi-component injection systems may mix injectablecomponents (e.g., liquids, solid, and/or powders) before injection.Several multiple chamber injection systems configured to mix andinjection multiple components are disclosed in U.S. Utility patentapplication Ser. No. 14/696,342, which was previously incorporated byreference herein.

Moreover, an increasing number of injectable liquids (e.g., medicines)have an additional requirement that two or more components arepreferably injected serially (e.g., into a patient) within a short time(e.g., seconds) of each other. Multiple components can be injectedserially using separate injection devices (e.g., pre-loaded syringes) orusing the same injection device to serially draw the multiple componentsfrom separate open containers and serially inject them. However, suchserial injection using separate injection devices or serially drawingand injecting the multiple components necessarily results in multipleneedle insertions into a patient, and can be inaccurate and lead to lossof components. Further, serial injection using separate injectiondevices or serially drawing the multiple components into a syringe canlead to unnecessary exposure of a user to one or more uncapped needles.Moreover, serial injection using separate injection devices or seriallydrawing and injecting the multiple components can cause an unacceptablelag between injections of the multiple components. Several multiplechamber injection systems that address these serial injection issues aredisclosed in U.S. Provisional Patent Application Ser. No. 62/682,381,which was previously incorporated by reference herein.

In addition, an increasing number of injectable liquids (e.g.,medicines) have yet another requirement that time of exposure of theinjectable liquid to metals (e.g., stainless steel of a needle) beminimized. Still another requirement is the desirability of systemssuitable for patient self-injection.

It is also desirable to incorporate needle stick prevention technologyinto the injection system. The ability to retract the sharp end of theneedle at least partially inside of the syringe protects the persongiving the injection and the patient from inadvertent needle stickinjuries.

There is a need for injection systems which address the shortcomings ofcurrently-available configurations. In particular, there is a need formultiple chamber safety injection solutions which may utilize theexisting and relatively well- controlled supply chain of conventionallydelivered prefilled syringe assemblies such as those described inreference to FIGS. 5A and 5B.

SUMMARY

Embodiments are directed to injection systems. In particular, theembodiments are directed to multiple chamber safe injection systems thatmove the needle into a protected configuration to minimize accidentaluser injury and contamination with used needles.

In one embodiment, a method for preparing a pre-filled multi-chamberinjection system includes providing an injection system body, theinjection system body defining an open proximal end, a body interior,and an open distal end. The method also includes introducing a firstsubstance into a distal end of the body interior. The method furtherincludes disposing a distal stopper member in the body interior throughthe open proximal end of the injection system body, the distal stoppermember and the injection system body defining proximal and distalchambers in the body interior, wherein the first substance is disposedin the distal chamber. Moreover, the method includes introducing asecond substance into the body interior. In addition, the methodincludes disposing a proximal stopper member in the body interiorthrough the open proximal end of the injection system body, such thatthe proximal stopper member defines a proximal end of the proximalchamber, wherein the second substance is disposed in the proximalchamber. The method also includes inserting an elongate member at leastpartially into the body interior, the elongate member having a pluralityof flow channels for fluidly coupling the proximal and distal chambersand a proximal end configured to penetrate the distal stopper member.The method further includes coupling a plunger member to the proximalstopper member.

In one or more embodiments, introducing the first substance into thedistal end of the body interior includes introducing a liquid into thedistal end of the body interior and lyophilizing the liquid. Introducingthe first substance into the distal end of the body interior may includeintroducing a powder or solid into the distal end of the body interior.The method may include disposing the injection system body in a rack ina first configuration before disposing the distal stopper member in thebody interior, where, when the injection system body is in the firstconfiguration, the distal end of the injection system body is pointed ina downward direction. The method may also include turning the injectionsystem body in the rack to a second configuration before introducing thefirst substance into the distal chamber through the open distal end,where, when the injection system body is in the first configuration, theproximal end of the injection system body is pointed in a downwarddirection. The method may include returning the injection system body inthe rack to the first configuration before introducing a secondsubstance into the body interior and disposing the proximal stoppermember in the body.

In one or more embodiments, the rack includes a feature to hold theinjection method body in the first and second configurations in therack. The distal stopper member may include a funnel therein, the methodfurther including the funnel guiding the needle proximal end to a centerof the distal stopper member. The funnel may include a U-shapedretaining member/detent. The needle proximal end may include a 3Darrowhead shape, the method further including the 3D arrowheadinterfering with the U-shaped retaining member/detent to temporarilyprevent distal movement of the distal stopper member. The method mayinclude lyophilizing the first substance in distal chamber beforecoupling the needle hub assembly to the distal end of the injectionsystem body.

In one or more embodiments, the method includes utilizing a pressuredifferential on proximal and distal sides of the proximal stopper memberto insert the proximal stopper member into the body interior through theopen proximal end of the injection system body. The method may includemaintaining a vacuum in the proximal chamber during insertion of theproximal stopper member into the body interior through the open proximalend of the injection system body. The method may include disposing theproximal stopper member above the open proximal end of the injectionsystem body before inserting the proximal stopper member into the bodyinterior. The method may include disposing a tube adjacent the proximalstopper member such that the proximal chamber is fluidly coupled to anatmosphere during insertion of the proximal stopper member into the bodyinterior through the open proximal end of the injection system body. Themethod may include maintaining a vacuum in the distal chamber during themethod. The method may include performing one or more steps of themethod in a vacuum.

In one or more embodiments, the method includes coupling a flange to theinjection system body such that the flange is preventing from movingalong a longitudinal axis and the plunger is moveable on thelongitudinal axis relative to the flange. The method may includecoupling the plunger to the proximal stopper member to facilitatemovement of the proximal stopper member along the longitudinal axis. Theinjection system body, the needle hub assembly, and the proximal anddistal stopper members may be pre-sterilized. The method may includepreparing a plurality of pre-filled multi-chamber injection systems. Themethod may include introducing a third substance into the body interiorthrough the open proximal end, and disposing a second proximal stoppermember in the body interior through the open proximal end of theinjection system body, such that the second proximal stopper memberdefines a proximal end of a second proximal chamber, where the thirdsubstance is disposed in the second proximal chamber.

In one embodiment, a method for preparing a pre-filled multi-chamberinjection system includes disposing an injection system body(syringe/cartridge) in a rack in a first configuration, the injectionsystem body defining an open proximal end, a body interior, and an opendistal end, where, when the injection system body is in the firstconfiguration, the distal end of the injection system body is pointed ina downward direction. The method also includes disposing a distalstopper member in the body interior through the open proximal end of theinjection system body, the distal stopper member and the injectionsystem body defining proximal and distal chambers in the body interior.The method further includes turning the injection system body in therack to a second configuration, in which the proximal end of theinjection system body is pointed in the downward direction. Moreover,the method includes introducing a first substance into the distalchamber through the open distal end. In addition, the method includescoupling a needle hub assembly to the distal end of the injection systembody, the needle hub assembly including a needle having a needleproximal end, such that the needle proximal end interferes with thedistal stopper member to temporarily prevent distal movement of thedistal stopper member. The method also includes returning the injectionsystem body in the rack to the first configuration. The method furtherincludes introducing a second substance into the body interior throughthe open proximal end. Moreover, the method includes disposing aproximal stopper member in the body interior through the open proximalend of the injection system body, such that the proximal stopper memberdefines a proximal end of the proximal chamber, where the secondsubstance is disposed in the proximal chamber.

In another embodiment, a method for preparing a pre-filled multi-chamberinjection system includes coupling a needle hub assembly to an injectionsystem body (syringe/cartridge), the needle hub assembly including aneedle having a needle proximal end, and the injection system bodydefining an open proximal end, a body interior, and a distal end closedby the needle hub assembly. The method also includes disposing theinjection system body in a rack in a first configuration, where, whenthe injection system body is in the first configuration, the distal endof the injection system body is pointed in a downward direction. Themethod further includes introducing a first substance into the bodyinterior through the open proximal end. Moreover, the method includesdisposing a distal stopper member in the body interior through the openproximal end of the injection system body, the distal stopper member andthe injection system body defining proximal and distal chambers in thebody interior, such that the needle proximal end interferes with thedistal stopper member to temporarily prevent distal movement of thedistal stopper member, where the first substance is disposed in thedistal chamber. In addition, the method includes introducing a secondsubstance into the syringe interior through the open proximal end. Themethod also includes disposing a proximal stopper member in the bodyinterior through the open proximal end of the injection system body,such that the proximal stopper member defines a proximal end of theproximal distal chamber, where the second substance is disposed in theproximal chamber.

In still another embodiment, a method for preparing a pre-filledmulti-chamber cartridge includes disposing a cartridge body in a rack ina first configuration, the cartridge body defining an open proximal end,a body interior, and an open distal end. When the cartridge body is inthe first configuration, the distal end of the cartridge body is pointedin a downward direction. The method also includes disposing a distalstopper member in the body interior through the open proximal end of thecartridge body, the distal stopper member and the cartridge bodydefining proximal and distal chambers in the body interior. The methodfurther includes turning the cartridge body in the rack to a secondconfiguration, in which the proximal end of the cartridge body ispointed in the downward direction. Moreover, the method includesintroducing a first substance into the distal chamber through the opendistal end. In addition, the method includes optionally coupling acartridge cap to the distal end of the cartridge body. The method alsoincludes coupling a needle hub assembly to the distal end of thecartridge body over the cartridge cap, the needle hub assembly includinga needle having a needle proximal end, such that the needle proximal endinterferes with the distal stopper member to temporarily prevent distalmovement of the distal stopper member. The method further includesreturning the cartridge body in the rack to the first configuration.Moreover, the method includes introducing a second substance into thebody interior through the open proximal end. In addition, the methodincludes disposing a proximal stopper member in the body interiorthrough the open proximal end of the cartridge body, such that theproximal stopper member defines a proximal end of the proximal chamber,where the second substance is disposed in the proximal chamber.

In yet another embodiment, a method for preparing a pre-filledmulti-chamber cartridge includes optionally coupling a cartridge cap toa cartridge body, the cartridge body defining an open proximal end, abody interior, and a distal end closed by the cartridge cap. The methodalso includes coupling a needle hub assembly to the distal end of thecartridge body over the cartridge cap, the needle hub assembly includinga needle having a needle proximal end. The method further includesdisposing the cartridge body in a rack in a first configuration, where,when the cartridge body is in the first configuration, the distal end ofthe cartridge body is pointed in a downward direction. Moreover, themethod includes introducing a first substance into the body interiorthrough the open proximal end. In addition, the method includesdisposing a distal stopper member in the body interior through the openproximal end of the cartridge body, the distal stopper member and thecartridge body defining proximal and distal chambers in the bodyinterior, such that the needle proximal end interferes with the distalstopper member to temporarily prevent distal movement of the distalstopper member, where the first substance is disposed in the distalchamber. The method also includes introducing a second substance intothe syringe interior through the open proximal end. The method furtherincludes disposing a proximal stopper member in the body interiorthrough the open proximal end of the cartridge body, such that theproximal stopper member defines a proximal end of the proximal chamber,where the second substance is disposed in the proximal chamber.

In another embodiment, a method for preparing a pre-filled multi-chambercartridge includes optionally coupling a cartridge cap to a cartridgebody, the cartridge body defining an open proximal end, a body interior,and a distal end closed by the cartridge cap. The method also includesdisposing the cartridge body in a rack in a first configuration, where,when the cartridge body is in the first configuration, the distal end ofthe cartridge body is pointed in a downward direction. The methodfurther includes introducing a first substance into the body interiorthrough the open proximal end. Moreover, the method includes disposing adistal stopper member in the body interior through the open proximal endof the cartridge body, the distal stopper member and the cartridge bodydefining proximal and distal chambers in the body interior, such thatthe needle proximal end interferes with the distal stopper member totemporarily prevent distal movement of the distal stopper member, wherethe first substance is disposed in the distal chamber. In addition, themethod includes coupling a needle hub assembly to the distal end of thecartridge body over the cartridge cap, the needle hub assembly includinga needle having a needle proximal end, such that the needle proximal endpierces the cartridge cap. The method also includes introducing a secondsubstance into the syringe interior through the open proximal end. Themethod further includes disposing a proximal stopper member in the bodyinterior through the open proximal end of the cartridge body, such thatthe proximal stopper member defines a proximal end of the proximalchamber, where the second substance is disposed in the proximal chamber.

In still another embodiment, a method for preparing a pre-filledmulti-chamber cartridge includes disposing a cartridge body in a rack ina first configuration, the cartridge body defining an open proximal end,a body interior, and an open distal end. When the cartridge body is inthe first configuration, the distal end of the cartridge body is pointedin a downward direction. The method also includes disposing a distalstopper member in the body interior through the open proximal end of thecartridge body, the distal stopper member and the cartridge bodydefining proximal and distal chambers in the body interior. The methodfurther includes turning the cartridge body in the rack to a secondconfiguration, in which the proximal end of the cartridge body ispointed in the downward direction. Moreover, the method includesintroducing a first substance into the distal chamber through the opendistal end. In addition, the method includes coupling a cartridge cap tothe distal end of the cartridge body, the cartridge cap including atransfer tube, such that the transfer tube interferes with the distalstopper member to temporarily prevent distal movement of the distalstopper member. The method also includes returning the cartridge body inthe rack to the first configuration. The method further includesintroducing a second substance into the body interior through the openproximal end. Moreover, the method includes disposing a proximal stoppermember in the body interior through the open proximal end of thecartridge body, such that the proximal stopper member defines a proximalend of the proximal chamber, where the second substance is disposed inthe proximal chamber.

In yet another embodiment, a method for preparing a pre-filledmulti-chamber cartridge includes optionally coupling a cartridge cap toa cartridge body, the cartridge body defining an open proximal end, abody interior, and a distal end closed by the cartridge cap. The methodalso includes piercing the cartridge cap with a transfer tube. Themethod further includes disposing the cartridge body in a rack in afirst configuration, where, when the cartridge body is in the firstconfiguration, the distal end of the cartridge body is pointed in adownward direction. Moreover, the method includes introducing a firstsubstance into the body interior through the open proximal end. Inaddition, the method includes disposing a distal stopper member in thebody interior through the open proximal end of the cartridge body, thedistal stopper member and the cartridge body defining proximal anddistal chambers in the body interior, such that the transfer tubeinterferes with the distal stopper member to temporarily prevent distalmovement of the distal stopper member, where the first substance isdisposed in the distal chamber. The method also includes introducing asecond substance into the syringe interior through the open proximalend. The method further includes disposing a proximal stopper member inthe body interior through the open proximal end of the cartridge body,such that the proximal stopper member defines a proximal end of theproximal chamber, where the second substance is disposed in the proximalchamber.

In one or more embodiments, the method includes coupling a flange and aplunger member to the injection system body such that the flange ispreventing from moving along a longitudinal axis and the plunger ismoveable on the longitudinal axis.

In still another embodiment, an autoinjector system includes adisposable injection system (syringe/cartridge) and a reusable drivesystem. The disposable injection system includes an injection systembody having proximal and distal ends, and an injection system bodyinterior therebetween. The disposable injection system also includes astopper member disposed in the injection system body interior. Thedisposable injection system further includes a plunger member coupled tothe stopper member. Moreover, the disposable injection system includes afinger flange coupled to the injection system body at the proximal endthereof. In addition, the disposable injection system includes a needlehub assembly coupled to the injection system body at the distal endthereof. The disposable injection system also includes a rigid needleshield coupled to the needle hub assembly. The reusable drive systemincludes a drive system body having a drive system body interior. Thedisposable injection system also includes a plunger actuator/pusher tomove the plunger member distally relative to the injection system bodywhen the injection system is mounted in the drive system. The disposableinjection system further includes a flange holder/carriage to move theinjection system distally and/or proximally relative to the drive systembody when the injection system is mounted in the drive system.

In one or more embodiments, the drive system includes a first motor tomove the plunger actuator/pusher, a second motor to move the flangeholder/carriage, a controller operatively coupled to the first andsecond motors, a display operatively coupled to the controller, and asensor operative coupled to the controller. The sensor may be selectedfrom the group consisting of an accelerometer, a contact sensor, aposition sensor, a gyroscope, a thermometer, and a skin contact sensor.The drive system may include a plurality of sensors.

In yet another embodiment, an autoinjector system includes a disposableinjection system (syringe/cartridge) and a reusable drive system. Thedisposable injection system includes an injection system body havingproximal and distal ends, and an injection system body interiortherebetween, The disposable injection system also includes first andsecond stopper members disposed in the injection system body interior,the first stopper member and the injection system body defining a firstchamber, the first and second stopper members and the injection systembody defining a second chamber. The disposable injection system furtherincludes a plunger member coupled to the second stopper member.Moreover, the disposable injection system includes a finger flangecoupled to the injection system body at the proximal end thereof. Inaddition, the disposable injection system includes a needle hub assemblycoupled to the injection system body at the distal end thereof. Thedisposable injection system also includes a rigid needle shield coupledto the needle hub assembly. The reusable drive system includes a drivesystem body having a drive system body interior. The reusable drivesystem also includes a plunger actuator/pusher to move the plungermember distally relative to the injection system body when the injectionsystem is mounted in the drive system. The reusable drive system furtherincludes a flange holder/carriage to move the injection system distallyand/or proximally relative to the drive system body when the injectionsystem is mounted in the drive system.

In one or more embodiments, the drive system includes a first motor tomove the plunger actuator/pusher, a second motor to move the flangeholder/carriage, a controller operatively coupled to the first andsecond motors, a display operatively coupled to the controller, and asensor operative coupled to the controller. The sensor may be selectedfrom the group consisting of accelerometer, a contact sensor, a positionsensor, a gyroscope, a thermometer, and a skin contact sensor. The drivesystem may include a plurality of sensors.

In another embodiment, a method for automatically mixing and injectingsubstances includes providing the autoinjector system described abovewith the injection system mounted in the drive system, and the plungeractuator/pusher and flange holder/carriage in a proximal first position.The method also includes the controller causing the first motor to movethe plunger actuator and the plunger member and the second stoppermember operatively coupled thereto distally relative to the injectionsystem body to transfer a fluid from the second chamber to the firstchamber to form an injectable medicine. The method further includes thecontroller causing the first motor to move the plunger actuator and theplunger member and the second stopper member operatively coupled theretofurther distally relative to the injection system body to inject theinjectable medicine through the needle hub assembly.

In one or more embodiments, the method includes the controller causingthe display to render a message instructing a user to agitate the deviceto enhance mixing of the fluid with a powder in the first chamber toform the injectable medicine. The method may include the controllercausing the display to render a message instructing the user to pointthe autoinjector system in an upward position and remove the rigidneedle shield from the autoinjector system before the controller causesthe first motor to move the plunger actuator and the plunger member andthe second stopper member operatively coupled thereto further distallyrelative to the injection system body. The method may include the sensordetecting the upward position of the autoinjector system; and thecontroller causing the second motor to move the flange holder/carriageproximally relative to the drive system body to separate the rigidneedle shield from the needle hub assembly only when the sensor detectsthe upward position of the autoinjector system.

In one or more embodiments, the method includes the controller causingthe display to render a message instructing the user to position theautoinjector system in contact with a patient before the controllercauses the first motor to move the plunger actuator and the plungermember and the second stopper member operatively coupled thereto furtherdistally relative to the injection system body. The method may includethe sensor detecting contact between the autoinjector system and thepatient, and the controller causing the first motor to move the plungeractuator and the plunger member and the second stopper memberoperatively coupled thereto further distally relative to the injectionsystem body only when the sensor detects the contact between theautoinjector system and the patient. The method may include thecontroller causing the display to render a message indicating an end ofinjection and instructing the user to remove the injection system afterthe controller causes the first motor to move the plunger actuator andthe plunger member and the second stopper member operatively coupledthereto further distally relative to the injection system body.

In still another embodiment, a multiple chamber safe injection systemincludes a syringe body defining a syringe body interior and a distalcoupling member at a distal end thereof. The system includes proximaland distal stopper members disposed in the syringe body interior,forming a proximal chamber between the proximal and distal stoppermembers and a distal chamber between the distal stopper member and thedistal end of the syringe body. The system also includes a plungermember configured to be manually manipulated to insert the proximalstopper member relative to the syringe body. The system further includesa mix tube disposed in the syringe body interior. Moreover, the systemincludes a vent plug disposed at least partially in the distal couplingmember and defining a plurality of channels configured to allow a gas toexit the syringe body interior while forming a liquid tight seal.

In yet another embodiment, an injection system includes a syringe bodydefining a proximal opening at a proximal end thereof and a distalneedle interface at a distal end thereof. The system also includesproximal and distal stopper members disposed in the syringe body,forming a proximal drug chamber between the proximal and distal stoppermembers and a distal drug chamber between the distal stopper member andthe distal end of the syringe body. The system further includes aplunger member configured to be manually manipulated to insert theproximal stopper member relative to the syringe body, where the plungermember has a smooth exterior surface. Moreover, the system includes afluid conveying assembly. In addition, the system includes a fingerflange including an anti-retraction mechanism. The anti-retractionmechanism has a brake tab configured to provide an opposing force to theplunger member to prevent proximal movement thereof relative to thebrake tab, and a retention feature configured to maintain theanti-retraction mechanism in a recess in the finger flange.

In one or more embodiments, the finger flange also includes anotherrecess configured to mount the finger flange on a flange of the syringebody. The anti-retraction mechanism may also include a plurality of fittabs configured to reduce a tolerance between the recess and a dimensionof the anti-retraction mechanism. The anti-retraction mechanism may be ametal clip.

In one or more embodiments, the brake tab is an elastic andself-energizing pawl. The brake tab may be disposed at an acute angle ina distal direction relative to a plane of the anti-retraction mechanism.The acute angle and an elasticity of the brake tab may increase africtional force against the plunger member upon retraction in aproximal direction. The acute angle of the brake tab also creates areaction force parallel to the plunger member, exerted by a sharp curvededge of the brake tab contacting the surface of the plunger member. Thisforce also prevents the plunger member from moving in the proximaldirection. The acute angle and an elasticity of the brake tab may causethe brake tab to exert an outward force through the anti-retractionmechanism to an inner wall of the finger flange when the plunger memberis retracted in a proximal direction.

In one or more embodiments, the finger flange also includes an openinghaving an edge configured to interfere with and retain theanti-retraction mechanism in the recess. The anti-retraction mechanismmay have a “C” or “O” shape. The anti-retraction mechanism may preventremoval of the plunger member from the syringe body after the plungermember has been inserted into the syringe body. The opposing force mayinclude a frictional force and a reaction force. The brake tab may beconfigured to penetrate the smooth exterior surface of plunger memberwhen the plunger member moves proximally relative to anti-retractionmechanism.

The aforementioned and other embodiments of the invention are describedin the Detailed Description which follows.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other aspects of embodiments are described in furtherdetail with reference to the accompanying drawings, in which the sameelements in different figures are referred to by common referencenumerals, wherein:

FIGS. 1A to 5C illustrate various aspects of conventional injectionsyringe configurations.

FIGS. 6A and 6B illustrate various aspects of syringe based dual chambersafe injection systems wherein a distal needle end/tip may be withdrawninto a protected configuration after use according to some embodiments.

FIGS. 7A to 7P illustrate various aspects of syringe based dual chambersafe injection systems during steps in methods for mixing and injectingusing same according to some embodiments.

FIGS. 8A and 8B illustrate various aspects of syringe based dual chambersafe injection systems according to some embodiments.

FIGS. 9A to 9C illustrate various aspects of a distal stopper memberhaving a stopper bushing with a detent for use with syringe based dualchamber safe injection systems according to some embodiments.

FIGS. 10A to 10C illustrate various aspects of a stopper member bushingwith a detent for use with syringe based dual chamber safe injectionsystems according to some embodiments.

FIGS. 11A to 11C illustrate various aspects of a detent for use with astopper member bushing for use with syringe based dual chamber safeinjection systems according to some embodiments.

FIGS. 12A to 12C depict a rack containing a plurality of injectionsystem/syringe bodies and stored in a container according to someembodiments.

FIG. 13 is a flow chart illustrating a method formanufacturing/assembling a multiple chamber safe injection systemaccording to some embodiments.

FIGS. 14A to 14J illustrate various steps in a method formanufacturing/assembling a multiple chamber safe injection systemaccording to some embodiments.

FIGS. 15A to 15D illustrate various aspects of a detent for use with astopper member bushing for use with a multiple chamber safe injectionsystem according to some embodiments.

FIGS. 16 and 16A illustrate an interaction between a detent and a needleproximal end according to some embodiments.

FIG. 17 depicts a rack containing a plurality of injectionsystem/syringe bodies and stored in a container according to someembodiments.

FIG. 18 is a flow chart illustrating a method formanufacturing/assembling a multiple chamber safe injection systemaccording to some embodiments.

FIGS. 19A to 19H illustrate various steps in a method formanufacturing/assembling a multiple chamber safe injection systemaccording to some embodiments.

FIGS. 20A to 20D depict a rack containing a plurality of cartridgebodies and stored in a container according to some embodiments.

FIG. 21 is a flow chart illustrating a method formanufacturing/assembling a multiple chamber safe injection systemaccording to some embodiments.

FIGS. 22A to 22J illustrate various steps in a method formanufacturing/assembling a multiple chamber safe injection systemaccording to some embodiments.

FIGS. 23A and 23B depict various aspects of a cartridge cap for use witha multiple chamber safe injection system according to some embodiments.

FIGS. 24A and 24B depict cartridge bodies for use with multiple chambersafe injection systems according to some embodiments.

FIG. 25 depicts a rack containing a plurality of cartridge bodies andstored in a container according to some embodiments.

FIG. 26 is a flow chart illustrating a method formanufacturing/assembling a multiple chamber safe injection systemaccording to some embodiments.

FIGS. 27A to 27G illustrate various steps in a method formanufacturing/assembling a multiple chamber safe injection systemaccording to some embodiments.

FIG. 28 is a flow chart illustrating a method formanufacturing/assembling a multiple chamber safe injection systemaccording to some embodiments.

FIGS. 29A to 29H illustrate various steps in a method formanufacturing/assembling a multiple chamber safe injection systemaccording to some embodiments.

FIG. 30 depicts cartridge stoppers for use with multiple chamber safeinjection systems according to some embodiments.

FIGS. 31A to 31H illustrate various steps in a method for injecting adrug using an autoinjector according to some embodiments.

FIGS. 32A to 32J illustrate various steps in a method for mixing drugcomponents and injecting the mixed drug using an autoinjector accordingto some embodiments.

FIGS. 33 to 40 illustrate various steps in a method for mixing drugcomponents and injecting the mixed drug using a syringe having a luerconnector according to some embodiments.

FIGS. 41 to 47 illustrate various aspects of a multiple chamber safeinjection system having a vent plug according to some embodiments.

FIG. 48 depicts a vent plug according to some embodiments.

FIGS. 41A and 49 to 56 depict anti-retraction mechanisms according tosome embodiments.

In order to better appreciate how to obtain the above-recited and otheradvantages and objects of various embodiments, a more detaileddescription of embodiments is provided with reference to theaccompanying drawings. It should be noted that the drawings are notdrawn to scale and that elements of similar structures or functions arerepresented by like reference numerals throughout. It will be understoodthat these drawings depict only certain illustrated embodiments and arenot therefore to be considered limiting of scope of embodiments.

DETAILED DESCRIPTION OF ILLUSTRATED EMBODIMENTS Exemplary Prefilled DualChamber Safe Injection Systems

Referring to FIGS. 6A and 6B, a perspective and a longitudinalcross-section view of a prefilled dual chamber safe injection system(100) are shown, with a conventional off-the-shelf prefilled syringebody (34) with conventional proximal and distal stopper members (32, 36)disposed therein. The proximal and distal stopper members (32, 36)together with the syringe body (34) define proximal and distal chambers(40, 42). The proximal and distal stopper members (36, 37) occlude theproximal and distal ends of the proximal chamber (40). The distalstopper member (36) occludes a proximal end of the distal chamber (42).In some embodiments, the distal end of the proximal stopper member (32)and the proximal end of the distal stopper member (36) may be coatedwith a lubricious polymer coating (e.g., PTFE), the first and secondpolymer coatings of the proximal and distal stopper members (32, 36),together with the syringe body (34) define the proximal chamber (40).The lubricious polymer coating also serves to isolate the rubber of theproximal and distal stopper members (32, 36) from the second liquid(254). The proximal and distal stopper members (32, 36) may be orientedas shown in FIGS. 6A and 6B or the distal stopper (36) may be flipped sothe lubricious coating faces the distal chamber (42) such that the firstliquid (252) in the distal chamber (42) contacts the lubricious coatingfor storage.

A needle coupling assembly (606) is disposed at the distal end of thedistal chamber (42) with a needle cover member (63) installed forstorage. The dual chamber safe injection system facilitates sequentialinjection of a first liquid (252) from the distal chamber (42) followedby injection of a second liquid (254) from the proximal chamber subjectto sequential insertion of a plunger assembly (44) relative to thesyringe body (34) to various degrees by a user. The plunger assembly(44) includes the proximal stopper member (32), a plunger housing member(69) and a plunger manipulation interface (128). The first and secondliquids located in the distal and proximal chambers (42, 40)respectively may be any liquid or gel, such as aqueous or oil basedmedicine solutions.

The dual chamber safe injection system (100) has a staked needleconfiguration wherein upon presentation to the user, a needle assembly,including a needle spine assembly (“needle”) (76) and a needle couplingassembly (606) are mounted in position ready for injection after removalof a needle cover member (63) which may comprise an elastomeric sealingmaterial on its internal surface to interface with a needle distal end(78) and/or a distal housing portion during storage. Alternatively, theneedle cover member (63) may comprise a vent (not shown) for allowingpressure resulting from the transfer of the liquids (252, 254) to escapefrom inside the syringe body (34) while preventing contamination fromentering the syringe body (34). While, the staked needle is depicted asmounted in position, the staked needle may be removably coupled to thesyringe body (34) using a Luer slip or a Luer lock interface (notshown), with the proximal end (50) of the needle member extendingthrough the Luer interface and into the distal chamber (42).Alternatively, the needle may be fixedly or removably mounted to theflange on a cartridge body instead of a syringe. Such cartridgeinjection systems are disclosed in U.S. Utility Patent ApplicationSerial Number 15/801,281, which was previously incorporated by referenceherein. In the embodiments depicted in FIGS. 6A and 6B, a significantportion of the safe needle retraction hardware resides within a plungerhousing.

Referring to FIGS. 7A-7L, various aspects of configurations designed tofacilitate injection of multi-part medications and retractions of aneedle into a syringe body are illustrated, wherein two or moremedication components are combined to form an injection combination orsolution shortly before delivery into the patient. In one variation, aliquid first medicine component/diluent (252) may be combined with asubstantially non-liquid second medicine component (254), such as apowdered and/or a solid (e.g., compressed powder) form, of a drug agent,such as a freeze-dried or lyophilized drug component, shortly beforeinjection. The second medicine component (254) may be comprised ofpowdered medicine formed into a generally solid form. The solid form maybe created by compressing powder and/or by using a binder material. Thissolid medicine component may be configured to be, cylindrical, tubular,spherical, a polygon, and/or or a toroidal shape. The solid medicine(254) may be placed inside the distal medicine chamber (42) duringand/or in place of the lyophilization step. The solid form of the secondmedicine component (254) is configured to dissolve and/or disperse whencontacted by liquid. The configurations described herein in reference toFIGS. 7A-7L relate to dual-chamber configurations, wherein two or morechambers within the same syringe body (34) are utilized to carry, mix,and inject an injection solution.

Referring to FIG. 7A and 7B, proximal and distal medicine chambers (40,42) are formed by a distal stopper member (36) in between two portionsof the interior of a syringe body (34), such that the distal medicinechamber (42) contains an air or gas gap, as well as a non-liquidmedication (254); a proximal medicine chamber (40), on the opposite sideof the distal stopper member (36) contains a liquid diluent (252), whichis proximally contained by a proximal stopper member (32). The liquiddiluent (252) is a first component of a medicine and the non-liquidmedication (254) is a second component of the medicine.

Referring to FIG. 7C, and the associated cross sectional view in FIG.7D, various components of a needle coupling assembly (here a so-called“staked” needle coupling assembly (606) is illustrated, but other needleassemblies as described below, including Luer-coupled as well as stakedconfigurations, may be utilized). Lug features (258) are configured toassist with coupling the needle coupling assembly (606) to a needlecover member (63), as shown in FIG. 7A, for example. A small O-ring maybe utilized as a sealing member (260) around the needle shaft, while alarger O-ring may be utilized as a sealing member (262) at the syringebody (34)/needle coupling assembly (606) interface. Alternatively, thesmall O-ring (260) and the large O-ring (262) may be combined into asingle seal that performs both of the O-ring sealing functions. Also,the small O-ring (260) may be used to seal both around the needle shaftand to the syringe body (34).

The needle includes a plurality (e.g., four) of proximal openings/ports(270) configured to allow for entry of a liquid diluent, to be expelledout of a more distally-located middle opening/aperture (266); a lumenplug (268) occludes the needle lumen to create the flow path from theproximal openings (270) to the middle opening (266) under conditionssuch as those described herein in reference to FIG. 7H. The needle alsoincludes a distal opening (264) on the opposite side of the lumen plug(268) from the middle opening (266). The distal opening (264) is fluidlycoupled to the needle distal end (48) through the needle to injectliquid into a patient.

Referring to FIG. 7E, a proximal harpoon interface (84) is configured toserially penetrate proximal and distal stopper members (32, 36), andcouple with a coupling feature (such as a needle retention feature areillustrated, for example, in FIGS. 7N and 7P, element 712) in theplunger rod. FIG. 7F illustrates a spike style harpoon couplinginterface (85) that is configured to serially pierce both proximal anddistal stopper members (32, 36) and couple with a coupling feature inthe plunger rod to retract the needle member at least partially into theplunger rod after the injection has been given to the patient.

FIGS. 7A, 7B, and 7G-7P illustrate a sequence of actions for aninjection procedure utilizing a dual chamber safe injection system suchas that described above. Referring to FIGS. 7A and 7B, an injectionassembly is in a stable configuration wherein it may be shipped orbrought to an injection patient care scenario; a first drugcomponent/liquid diluent (252) is isolated from a second non-liquid drugcomponent (254), both within a syringe body on opposite sides of adistal stopper member (36).

FIGS. 7G and 7H illustrate initial insertion movement of the plungerassembly (44), advancing the distal (36) and proximal (32) stoppermembers together relative to the syringe body (34). Referring to FIG.7H, with advancement sufficient to stab the proximal end (50) of theneedle assembly across the distal stopper member (36), a fluid pathwayis formed between the two previously isolated chambers (40, 42) of thesyringe body (34), such that the liquid first drug component (252) inthe proximal medicine chamber (40) may flow into at least one of theproximal openings (270), through the transfer pipe (46), and exit themore distal middle opening (266), to reach the non-liquid second drugcomponent (254) in the distal medicine chamber (42).

FIGS. 7I and 7J illustrate that with further insertion until the stoppermembers (36, 32) are immediately adjacent each other, the liquid firstdrug component/diluent (252) has moved into the distal medicine chamber(42) to join the non-liquid second drug component (254). FIGS. 7K and 7Lillustrate that with time and/or manual agitation, the liquid first drugcomponent/diluent (252) and previously non-liquid second drug component(254) become mixed to form a mixed medication solution (272).

In some embodiment, especially with lyophilized non-liquid second drugcomponents, the mixed medication solution (272) may be formed withminimal or no agitation or time passage. In another embodiment,especially with drugs which are held in suspension or emulsified drugs,vigorous shaking may be necessary to facilitate mixing. In the case ofvigorous shaking it is useful to the user to be able to remove theirthumb from the plunger manipulation interface (128). During transfer ofliquid first medicine component (252) from the proximal to the distalmedicine chambers (40, 42) pressure may build up in the distal medicinechamber (42). This pressure acts upon the proximal and distal stoppermembers (32, 36) to resist stopper motion. The pressure buildup may alsomove the stopper members (32, 36) and plunger manipulation interface(128) proximally if the user does not have their thumb restraining theplunger assembly (44). Mixed configuration latches or “mix clicks” inthe plunger assembly (44) (depicted in FIGS. 9A and 9B and describedbelow) may be utilized to provide resistance to plunger manipulationinterface (128) motion due to pressure buildup and allow the user torelease their thumb from the plunger manipulation interface (128) forshaking or mixing of the drug. The mix clicks may also provide anaudible and/or tactile indication that the transfer of liquid firstmedicine component (252) has been completed. The distal medicine chamber(42) may also include an agitation device, which assists in mixing ofthe medicine components.

With the assembly ready for injection of the mixed solution (272), theneedle cover member (63) may be removed and the patient may be injectedwith the exposed needle distal end (48) with depression/insertion of theplunger assembly (44) and associated stopper members (36, 32) as shownin FIGS. 7M and 7N. Referring to FIGS. 70 and 7P, with fulldepression/insertion of the plunger assembly (44) and associated stoppermembers (32, 36), the sharp needle distal end/point (48) mayautomatically retract at least partially through the distal and proximalstopper members (36, 32) to a safe position within either the syringebody (34), the needle coupling assembly (606), or at least partiallywithin the plunger assembly (44). Automatic retraction of the needle atleast partially within the plunger is described in U.S. utility patentapplication Ser. No. 14/696,342, which was previously incorporated byreference herein.

Further details regarding multiple chamber injection systems(components, methods using same, etc.) are disclosed in U.S. Utilitypatent application Ser. No. 15/801,259, and U.S. Provisional PatentApplication Ser. Nos. 62/682,381 and 62/729,880, which were allpreviously incorporated by reference herein.

Exemplary Distal Bushings with Detents in Dual Chamber Safe InjectionSystems

FIGS. 8A and 8B depict a prefilled dual chamber safe injection system(800) according to some embodiments. The system (800) includes a stopperbushing (810) having a detent (812) disposed therein (see FIG. 8B). Thedetent (812) is configured to interact with the sharpened proximal end(884) of the needle spine assembly (876) and a shoulder (816) at thejunction between the needle proximal end (850) and the needle joiningmember (883) to provide resistance to distal movement of the distalstopper member (836) relative to the needle spine assembly (876) (seeFIG. 8B).

The interaction between the detent (812) and the proximal end (884)maintains the distal stopper member (836) in a ready to use positionduring storage and transport, such as the configuration depicted inFIGS. 8A and 8B. This interaction will maintain the position of thedistal stopper member (836) even with a vacuum or partial vacuum (e.g.for the lyophilized component) in the distal chamber (842). Without thedetent (812) and with a vacuum in the distal chamber (842), the distalstopper member (836) will eventually move distally relative to theneedle spine assembly (876) and be penetrated thereby. This would renderthe system unusable.

The interaction between the detent (812) and the shoulder (816)maintains the distal stopper member (836) in a transfer position duringtransfer of the liquid from the proximal chamber (840) to the distalchamber (842). This interaction allows the user to apply a wider rangeof force to the plunger member to transfer the liquid while minimizingthe risk of premature movement of the distal stopper member (836).

FIGS. 9A to 9C depict the interactions between the detent (812) and thesharpened proximal end (884) of the needle spine assembly (876) and ashoulder (816) on the needle spine assembly (876) in the prefilled dualchamber safe injection system (800) depicted in FIGS. 8A and 8B. FIG. 9Ashows a distal stopper member (836) having a stopper bushing (810) witha detent (812) and defining an alignment funnel (814). In FIG. 9A thealignment funnel (814) guides a proximal end (884) of the needle spineassembly (876) into positioned adjacent the detent (812).

FIG. 9B shows the storage/transport configuration of the system (800).In this configuration, the sharpened proximal end (884) of the needlespine assembly (876) is disposed adjacent to and partially within thedetent (812). Various properties of the proximal end (884) and thedetent (812) (e.g., geometric, material, etc.) can be modified tomodulate the force required to push the proximal end (884) past thedetent (812). These properties are described in detail below. In oneembodiment, the force required to push the proximal end (884) past thedetent (812) is from about 2 pounds to about 5 pounds. As describedabove, even with a vacuum or partial vacuum in the distal chamber (842)urging the distal stopper member (836) in a distal direction, theinteraction between the proximal end (884) and the detent (812) preventspremature movement of the distal stopper member (836) relative to theneedle spine assembly (876). This allows the prefilled dual chambersystem (800) to be stored while minimizing the risk of prematuremovement of the distal stopper member (836), which can render the system(800) unusable.

FIG. 9C shows the transfer configuration of the system (800). In thisconfiguration, the distal stopper member (836) has been pushed distallypast the sharpened proximal end (884) of the needle spine assembly (876)by user provided force on the plunger member. The proximal openings(885) are disposed in the proximal chamber (840) allowing liquid totransfer from the proximal chamber (840) to the distal chamber (842).While a vacuum in the distal chamber (842) withdraw the liquid out ofthe proximal chamber (840), user generated force applied to the proximalstopper member (832) via the plunger member will assist the liquidtransfer. In this configuration, a shoulder (816) on the needle spineassembly (876) is disposed adjacent to the detent (812). Variousproperties of the shoulder (816) and the detent (812) (e.g., geometric,material, etc.) can be modified to modulate the force required to pushthe shoulder (816) past the detent (812). These properties are describedin detail below. In one embodiment, the force required to push theshoulder (816) past the detent (812) is from about 2 pounds to about 5pounds. The shoulder is formed at the joint between the needle proximalend (850) and the needle joining member (883). While the interactionbetween the shoulder (816) and the detent (812) holds the system (800)in the transfer configuration depicted in FIG. 9C, pressure applied tothe plunger member will aid liquid transfer from the proximal chamber(840) to the distal chamber (842). The force required to overcome theinterference between the shoulder (816) and the detent (812) providesmore latitude for a user to press the plunger member to aid in theliquid transfer. This increases the chances of complete liquid transfer.

FIGS. 10A to 10C depict a stopper bushing (810) for use with theprefilled dual chamber safe injection system (800) depicted in FIGS. 8Aand 8B. The stopper bushing (810) has a detent (812) inserted into aslot in the bushing (810) along an axis orthogonal to the longitudinalaxis of the needle spine assembly. As shown in FIG. 10C, the detent maybe made of a bent wire having a “U” shape.

FIGS. 11A to 11C show detents (1112, 1112′) for use with stopperbushings of prefilled dual chamber safe injection systems according tosome embodiments. The detents (1112, 1112′) are formed from a sheet ofmetallic material, and thus have a flat cross-section. The detents(1112, 1112′) all have a “U” shape and include a notch (1118) configuredto receive a round shape, such as those on sharpened proximal ends andshoulders of the needle spine assemblies. The detent (1112′) depicted inFIG. 11B includes a chamfered/baffled penetration surface (1120) arounda circumference of the notch (1118) on the side of the detent (1112′)adjacent the sharpened proximal ends of the needle spine assemblies inthe storage/transport configuration described above. The beveledpenetration surface (1120) can be modified to modulate the amount offorce required to penetrate the detent (1112′).

FIG. 11C depicts the sharpened proximal end (1184) of a needle spineassembly (1176) disposed in the notch (1118) of a detent (1112), such asin a storage/transport configuration.

In one embodiment, the resistance force provided by the detent (1112) asit slides over a sharpened proximal end (1184) of a needle spineassembly (1176) is variable. The detent (1112) resist penetration by theproximal end (1184) during storage (e.g., for several years). With theapplication of a predetermined amount of force by the user, the proximalend (1184) slides through the detent (1112). Then, the resistance forceto movement of the needle spine assembly (1176) through the detent(1112) is minimal until the detent (1112) reaches the shoulder (816, seeFIG. 9C). When the detent (1112) abuts the shoulder, resistance forceincreases to reliably stop the progress of the detent (1112) (and distalstopper member) relative to the needle (1176). After liquid transferdescribed above, the user applies another predetermined amount of forceto push the detent (1112) will over the shoulder. After the shoulder iscleared, the friction from the interaction of the detent (1112) and theneedle (1176) is minimal to facilitate giving the injection and needleretraction.

The predetermined amount of force can be modulated to accommodate acombination of the system function requirements and the aestheticimpression on the user. If the activation force is too low, it may work,but be too difficult for the user to apply the force lightly enough, andthe user may overshoot. If the force is too high, the user may find thatit is “too hard” to activate the system. Fortunately, the predeterminedamount of force can be “tune” a range by modifying various componentcharacteristics.

While the embodiments described above include dual chamber safetyinjection systems, the scope of the claims also include other multiplechamber safety injection systems. For multiple chamber safety injectionsystems with more than two chambers, more than two stopper members areinserted into an injection system body (e.g., syringe body, cartridgebody, etc.) to define a corresponding number of chambers.

Exemplary Multiple Chamber Safe Injection System Manufacturing Methods

Injection System/Syringe Fill Distal Chamber from Front

FIGS. 12A and 12B depict a rack 1210 containing a plurality of injectionsystem/syringe bodies 1410 and stored in a container 1212. The rack 1210and the container 1212 are made from materials that are sterilizable.The container 1212 is closable with a seal 1214 (FIG. 12A) to maintainthe sterility of the rack 1210 and injection system/syringe bodies 1410contained therein.

FIG. 12C depicts the rack 1210 removed from the container 1212 and oneinjection system/syringe body 1410 removed from the rack 1210. The rack1210 has a plurality of features (e.g., sleeves and/or flanges) 1216 tohold the injection system/syringe bodies 1410 in a first configurationin which the distal end of the injection system/syringe body 1410 ispointed in a generally downward direction (see FIG. 14A). In someembodiments, the features 1216 are also configured to hold the injectionsystem/syringe bodies 1410 in a second configuration in which theproximal end of the injection system/syringe body 1410 is pointed in agenerally downward direction (see FIG. 14C).

FIG. 13 depicts a method 1300 for manufacturing/assembling a multiplechamber safe injection system according to some embodiments.Corresponding partially assembled components are depicted in FIGS. 14Ato 14J.

At 1310, an injection system/syringe body 1410 is disposed in a rack ina first (downward) configuration as shown in FIG. 14A. The injectionsystem/syringe body 1410 may be disposed in the rack by a user (e.g.,using a tool) or by a mechanical device (e.g., robot).

At 1312, a distal stopper member 1414 is disposed in an interior 1412 ofthe injection system/syringe body 1410 as shown in FIG. 14B. The distalstopper member 1414 may be inserted by a user (e.g., using a tool) or bya mechanical device (e.g., robot). The distal stopper member 1414 andthe injection system/syringe body 1410 define proximal and distalchambers 1416, 1418 in the body interior 1412. The distal stopper member1414 may be positioned over an open proximal end of the injectionsystem/syringe body 1410 to facilitate insertion of the distal stoppermember 1414 into the body interior 1412.

At 1314, the injection system/syringe body 1410 is turned to a second(upward) configuration as shown in FIG. 14C. The injectionsystem/syringe body 1410 may be repositioned in the rack after beingturned to the second configuration. Injection system/syringe body 1410may be turned and/or repositioned by a user (e.g., using a tool) or by amechanical device (e.g., robot).

At 1316, a first substance 1420 is introduced into the distal chamber1418 through the open distal end of the injection system/syringe body1410 as shown in FIG. 14C. The first substance 1420 may be introduceddirectly through the opening at the distal end of the injectionsystem/syringe body 1410. In some embodiments, a tube may be insertedthrough the opening at the distal end of the injection system/syringebody 1410, and the first substance 1420 may be introduced through thetube. The first substance 1420 may be a liquid, a solid (e.g.,compressed powder), and/or a powder. In some embodiments where the firstsubstance 1420 is a liquid, the first substance 1420 may be lyophilizedin an optional step to form a powder as shown in FIG. 14D.

At 1318, a needle hub assembly 1422 is coupled to the distal end of theinjection system/syringe body 1410 as shown in FIGS. 14E and 14F. Theneedle hub assembly 1422 includes a needle 1424 having a needle proximalend 1426. The needle proximal end 1426 interferes with the distalstopper member 1414 to temporarily prevent distal movement of the distalstopper member 1414 relative to the injection system/syringe body 1410.The needle hub assembly 1422 is coupled to the distal end of theinjection system/syringe body 1410 by a user (e.g., using a tool) or bya mechanical device (e.g., robot). Alternatively, the injectionsystem/syringe body 1410 may be closed with a luer cap as disclosed inFIGS. 33-40 and described below. In this case the dual chamber systemwould be provided without a pre-attached needle. The transfer tubecomponent may be pre-inserted into the syringe body or installed at thetime of placing the luer cap. The user may attach a needle at the timeof use by using a luer slip or luer lock connection method.

In some alternative embodiments, the injection system/syringe body 1410may be supplied with a needle hub assembly 1422 or luer cap coupledthereto. In some embodiments, the coupled the injection system/syringebody 1410, needle hub assembly 1422, and/or luer cap may bepre-sterilized. In other embodiments, pre-sterilized components may besupplied and assembled at the time of filling.

Components of the distal stopper member 1414 that interfere with theneedle proximal end 1426 are depicted in FIGS. 15A to 15D and 16 to 16A.FIG. 15A depicts a U-shaped retaining member/detent 1428 and abushing/funnel 1430. After coupling the U-shaped retaining member/detent1428 the bushing/funnel 1430, the bushing/funnel 1430 is screwed intothe stopper member 1414. FIGS. 16 and 16A depict the stage in themanufacturing process identified at 1318 and also shown in FIG. 14F. Asshown in FIG. 16A, the needle proximal end 1426 has an enlarged portionthat interferes with the U-shaped retaining member/detent 1428. Thisinterference increases the amount of force necessary to move the needleproximal end 1426 past the distal stopper member 1414. The increasedamount of force allows a vacuum to be present in the distal chamber 1418of the injection system/syringe body 1410 without prematurely moving theneedle proximal end 1426 past the distal stopper member 1414 duringstorage of the multiple chamber safe injection system. The bushingfunnel 1430 guides the needle proximal end 1426 to the U-shapedretaining member/detent 1428 during assembly.

At 1320, the injection system/syringe body 1410 is turned back to thefirst (downward) configuration as shown in FIG. 14G. The injectionsystem/syringe body 1410 may be repositioned in the rack after beingturned back to the first configuration. Injection system/syringe body1410 may be turned and/or repositioned by a user (e.g., using a tool) orby a mechanical device (e.g., robot).

At 1322, a second substance 1432 is introduced into the proximal chamber1416 through the open proximal end of the injection system/syringe body1410 as shown in FIG. 14H. The second substance 1432 may be introduceddirectly through the opening at the proximal end of the injectionsystem/syringe body 1410. The second substance 1432 may be a liquid oranother fluid.

At 1324, a proximal stopper member 1434 is disposed in the interior 1412of the injection system/syringe body 1410 as shown in FIG. 141 . Theproximal stopper member 1434 may be inserted by a user (e.g., using atool) or by a mechanical device (e.g., robot). The proximal stoppermember 1434 closes the proximal chambers 1416 defined by the injectionsystem/syringe body 1410 and the distal stopper member 1414. Theproximal stopper member 1434 may be positioned over an open proximal endof the injection system/syringe body 1410 to facilitate insertion of theproximal stopper member 1434 into the body interior 1412.

A pressure differential on opposite sides of the proximal stopper member1434 may be used to draw the proximal stopper member into the bodyinterior 1412. For instance, a vacuum maybe formed on the distal side ofthe proximal stopper member 1434. In some embodiments, a small tube isdisposed adjacent the proximal stopper member 1434 to release pressurethat builds up as the proximal stopper member 1434 is inserted into thebody interior 1412. The small tube is removed after assembly.

In an optional step shown in FIG. 14J, a finger flange 1336 and aplunger member 1438 are coupled to the injection system/syringe body1410. The finger flange 1436 may be coupled to the injectionsystem/syringe body 1410 such that it is prevented from moving along alongitudinal axis of the body 1410 (e.g., by snapping over a glassflange at the proximal end of the body 1410). The plunger member 1438may be coupled to the injection system/syringe body 1410 such that it ismovable along a longitudinal axis of the body 1410. A distal end of theplunger member 1438 is also coupled to the proximal stopper member 1434(e.g., using a threaded screw), such that movement of the plunger member1438 relative to the injection system/syringe body 1410 moves theproximal stopper member 1434. The finger flange 1436 and a plungermember 1438 may be coupled to the injection system/syringe body 1410 bya user (e.g., using a tool) or by a mechanical device (e.g., robot).

Further details regarding the injection system/syringe body 1410, theproximal and distal stopper members 1414, 1434, the needle hub assembly1422, the finger flange 1436, and the plunger member 1438 are describedin U.S. Utility patent application Ser. No. 15/801,259, which waspreviously incorporated by reference herein. The method 1300 ofmanufacturing/assembling a multiple chamber safe injection systemdepicted in FIG. 13 may take place, fully or in part, in a vacuum (e.g.,vacuum chamber or vacuum room). The injection system/syringe body 1410,the proximal and distal stopper members 1414, 1434, the needle hubassembly 1422, the finger flange 1436, and the plunger member 1438 maybe pre-sterilized before assembly.

While a single multiple chamber safe injection system ismanufactured/assembled in the method 1300 depicted in FIGS. 13 and 14Ato 14J, the same method 1300 may be used to manufacture/assemble aplurality of multiple chamber safe injection systems either in parallelor in series. While the method 1300 depicted in FIGS. 13 and 14A to 14Jinvolves a dual chamber system with two stopper members 1414, 1434, insome embodiments, a third stopper member may be added to the multiplechamber safe injection system to define a third chamber using stepssimilar to those in 1322 and 1324 described above. In some embodiments,more than three stopper members and chambers may be formed in a multiplechamber safe injection system.

Injection System/Syringe Fill Distal Chamber from Back

FIG. 17 depicts a rack 1210 containing a plurality of injectionsystem/syringe bodies 1410 coupled to a plurality of needle hubassemblies 1422 and stored in a container 1212. The rack 1210 and thecontainer 1212 are made from materials that are sterilizable. Thecontainer 1212 is closable with a seal 1214 (see FIG. 12B) to maintainthe sterility of the rack 1210 and injection system/syringe bodies 1410and needle hub assemblies 1422 contained therein. The rack 1210 isremoved from the container 1212 and one injection system/syringe body1410 coupled to a needle hub assembly 1422 is removed from the rack1210. The rack 1210 has a plurality of features (e.g., sleeves and/orflanges) 1216 to hold the injection system/syringe bodies 1410 andneedle hub assemblies 1422 with the distal end of the injectionsystem/syringe body 1410 is pointed in a generally downward direction(see FIG. 19A).

FIG. 18 depicts a method 1800 for manufacturing/assembling a multiplechamber safe injection system according to some embodiments.Corresponding partially assembled components are depicted in FIGS. 19Ato 19H. The injection system/syringe body 1410, the proximal and distalstopper members 1414, 1434, the needle hub assembly 1422, the fingerflange 1436, and the plunger member 1438 may be the same systemcomponents depicted in FIGS. 14A to 16A and described above.

At 1810, a needle hub assembly 1422 is coupled to the distal end of theinjection system/syringe body 1410 as shown in FIG. 19A. The needle hubassembly 1422 includes a needle 1424 having a needle proximal end 1426.The needle hub assembly 1422 is coupled to the distal end of theinjection system/syringe body 1410 by a user (e.g., using a tool) or bya mechanical device (e.g., robot). In some alternative embodiments, theinjection system/syringe body 1410 may be supplied with the needle hubassembly 1422 coupled thereto. In some embodiments, the coupled theinjection system/syringe body 1410 and needle hub assembly 1422 may bepre-sterilized. In other embodiments, pre-sterilized components may besupplied and assembled at the time of filling.

At 1812, the injection system/syringe body 1410 coupled to the needlehub assembly 1422 is disposed in a rack with the injectionsystem/syringe body 1410 pointed downward as shown in FIGS. 17 and 19A.The injection system/syringe body 1410 may be disposed in the rack by auser (e.g., using a tool) or by a mechanical device (e.g., robot).Alternatively, the injection system/syringe body 1410 may be closed witha luer cap as disclosed in FIGS. 33-40 and described below. In this casethe dual chamber system would be provided without a pre-attached needle.The transfer tube component may be pre-inserted into the syringe body orinstalled at the time of placing the luer cap. The user may attach aneedle at the time of use by using a luer slip or luer lock connectionmethod.

At 1814, a first substance 1420 is introduced into the distal chamber1418 through the open proximal end of the injection system/syringe body1410 as shown in FIG. 19B. The first substance 1420 may be introduceddirectly through the opening at the proximal end of the injectionsystem/syringe body 1410. The first substance 1420 may be a liquid,solid (e.g., compressed powder), and/or a powder. In some embodimentswhere the first substance 1420 is a liquid, the first substance 1420 maybe lyophilized in an optional step to form a powder as shown in FIG.19C.

At 1816, a distal stopper member 1414 is disposed in an interior 1412 ofthe injection system/syringe body 1410 as shown in FIGS. 19D and 19E.The distal stopper member 1414 may be inserted by a user (e.g., using atool) or by a mechanical device (e.g., robot). The distal stopper member1414 and the injection system/syringe body 1410 define proximal anddistal chambers 1416, 1418 in the body interior 1412. The distal stoppermember 1414 may be positioned over an open proximal end of the injectionsystem/syringe body 1410 to facilitate insertion of the distal stoppermember 1414 into the body interior 1412 as shown in FIG. 19D.

The needle proximal end 1426 interferes with the distal stopper member1414 to temporarily prevent distal movement of the distal stopper member1414 relative to the injection system/syringe body 1410. Components ofthe distal stopper member 1414 that interfere with the needle proximalend 1426 are depicted in FIGS. 15A to 15D and 16 to 16A, and describedabove.

At 1818, a second substance 1432 is introduced into the proximal chamber1416 through the open proximal end of the injection system/syringe body1410 as shown in FIG. 19F. The second substance 1432 may be introduceddirectly through the opening at the proximal end of the injectionsystem/syringe body 1410. The second substance 1432 may be a liquid oranother fluid.

At 1820, a proximal stopper member 1434 is disposed in the interior 1412of the injection system/syringe body 1410 as shown in FIG. 19G. Theproximal stopper member 1434 may be inserted by a user (e.g., using atool) or by a mechanical device (e.g., robot). The proximal stoppermember 1434 closes the proximal chambers 1416 defined by the injectionsystem/syringe body 1410 and the distal stopper member 1414. Theproximal stopper member 1434 may be positioned over an open proximal endof the injection system/syringe body 1410 to facilitate insertion of theproximal stopper member 1434 into the body interior 1412. The proximalstopper member 1438 may be inserted using a pressure differential or asmall tube as described above.

In an optional step shown in FIG. 19H, a finger flange 1436 and aplunger member 1438 are coupled to the injection system/syringe body1410. The finger flange 1436 may be coupled to the injectionsystem/syringe body 1410 such that it is prevented from moving along alongitudinal axis of the body 1410 (e.g., by snapping over a glassflange at the proximal end of the body 1410). The plunger member 1438may be coupled to the injection system/syringe body 1410 such that it ismovable along a longitudinal axis of the body 1410. A distal end of theplunger member 1438 is also coupled to the proximal stopper member 1434(e.g., using a threaded screw), such that movement of the plunger member1438 relative to the injection system/syringe body 1410 moves theproximal stopper member 1434. The finger flange 1436 and a plungermember 1438 may be coupled to the injection system/syringe body 1410 bya user (e.g., using a tool) or by a mechanical device (e.g., robot).

While a single multiple chamber safe injection system ismanufactured/assembled in the method 1800 depicted in FIGS. 18 and 19Ato 19H, the same method 1800 may be used to manufacture/assemble aplurality of multiple chamber safe injection systems either in parallelor in series. While the method 1800 depicted in FIGS. 18 and 19A to 19Hinvolves a dual chamber system with two stopper members 1414, 1434, insome embodiments, a third stopper member may be added to the multiplechamber safe injection system to define a third chamber using stepssimilar to those in 1818 and 1820 described above. In some embodiments,more than three stopper members and chambers may be formed in a multiplechamber safe injection system.

Cartridge Fill Distal Chamber from Front

FIGS. 20A and 20B depict a rack 1210′ containing a plurality ofcartridges 1410′ and stored in a container 1212. The rack 1210′ and thecontainer 1212 are made from materials that are sterilizable. Thecontainer 1212 is closable with a seal 1214 (FIG. 20A) to maintain thesterility of the rack 1210′ and cartridges 1410′ contained therein.

FIG. 20C depicts the rack 1210′ removed from the container 1212 and onecartridge 1410′ removed from the rack 1210′. The rack 1210′ has aplurality of features (e.g., sleeves and/or flanges) 1216′ to hold thecartridges 1410′ in a first configuration in which the distal end of thecartridge 1410′ is pointed in a generally downward direction (see FIG.22A). In some embodiments, the features 1216′ are also configured tohold the cartridges 1410′ in a second configuration in which theproximal end of the cartridge 1410′ is pointed in a generally downwarddirection (see FIG. 22C).

FIG. 21 depicts a method 2100 for manufacturing/assembling a multiplechamber safe injection system according to some embodiments.Corresponding partially assembled components are depicted in FIGS. 22Ato 22J.

At 2110, a cartridge 1410′ is disposed in a rack in a first (downward)configuration as shown in FIG. 22A. The cartridge 1410′ may be disposedin the rack by a user (e.g., using a tool) or by a mechanical device(e.g., robot).

At 2112, a distal stopper member 1414 is disposed in an interior 1412 ofthe cartridge 1410′ as shown in FIG. 22B. The distal stopper member 1414may be inserted by a user (e.g., using a tool) or by a mechanical device(e.g., robot). The distal stopper member 1414 and the cartridge 1410′define proximal and distal chambers 1416, 1418 in the body interior1412. The distal stopper member 1414 may be positioned over an openproximal end of the cartridge 1410′ to facilitate insertion of thedistal stopper member 1414 into the body interior 1412.

At 2114, the cartridge 1410′ is turned to a second (upward)configuration as shown in FIG. 22C. The cartridge 1410′ may berepositioned in the rack after being turned to the second configuration.Cartridge 1410′ may be turned and/or repositioned by a user (e.g., usinga tool) or by a mechanical device (e.g., robot).

At 2116, a first substance 1420 is introduced into the distal chamber1418 through the open distal end of the cartridge 1410′ as shown in FIG.22C. The first substance 1420 may be introduced directly through theopening at the distal end of the cartridge 1410′. In some embodiments, atube may be inserted through the opening at the distal end of thecartridge 1410′, and the first substance 1420 may be introduced throughthe tube. The first substance 1420 may be a liquid, a solid (e.g.,compressed powder), and/or a powder. In some embodiments where the firstsubstance 1420 is a liquid, the first substance 1420 may be lyophilizedin an optional step to form a powder as shown in FIG. 22D.

At 2118, a cartridge cap 1440 and a needle hub assembly 1422′ arecoupled to the distal end of the cartridge 1410′ as shown in FIG. 22E.First, the cartridge cap 1440 may be coupled to the distal end of thecartridge 1410′ by a user (e.g., using a tool) or by a mechanical device(e.g., robot). Exemplary cartridge caps 1440 are shown in FIGS. 23A and23B. The cartridge caps 1440 include a crimp seal 1442 with an openingtherein and a septum 1444. The crimp seal 1442 may be made from aluminumand the septum 1444 may be made from rubber. The cartridge cap 1440 maybe coupled to the distal end of the cartridge 1410′ by crimping thecrimp seal 1442 around and enlarge portion of the cartridge 1410′ at adistal end thereof.

Next, the needle hub assembly 1422′ is coupled to the distal end of thecartridge 1410′ on top of the cartridge cap 1440 as shown in FIG. 22G.As shown in FIG. 22F, the needle hub assembly 1422′ includes a needle1424 having a needle proximal end 1426. The needle proximal end 1426interferes with the distal stopper member 1414 to temporarily preventdistal movement of the distal stopper member 1414 relative to thecartridge 1410′. The needle hub assembly 1422′ is coupled to the distalend of the cartridge 1410′ by a user (e.g., using a tool) or by amechanical device (e.g., robot). Components of the distal stopper member1414 that interfere with the needle proximal end 1426 are depicted inFIGS. 15A to 15D and 16 to 16A, and described above.

In some alternative embodiments, the cartridge 1410′ may be suppliedwith a needle hub assembly 1422′ or luer cap coupled thereto. In someembodiments, the coupled the cartridge 1410′, needle hub assembly 1422′,and/or luer cap may be pre-sterilized. In other embodiments,pre-sterilized components may be supplied and assembled at the time offilling.

While a cartridge cap 1440 is included in the embodiment depicted inFIG. 22E, the cartridge cap 1440 is optional and the needle hub assembly1422′ is directly coupled to the distal end of the cartridge 1410′ insome embodiments (compare FIGS. 24A (no cap) and 24B (with cap)).

At 2120, the cartridge 1410′ is turned back to the first (downward)configuration as shown in FIG. 22G. The cartridge 1410′ may berepositioned in the rack after being turned back to the firstconfiguration. Cartridge 1410′ may be turned and/or repositioned by auser (e.g., using a tool) or by a mechanical device (e.g., robot).

At 2122, a second substance 1432 is introduced into the proximal chamber1416 through the open proximal end of the cartridge 1410′ as shown inFIG. 22H. The second substance 1432 may be introduced directly throughthe opening at the proximal end of the cartridge 1410′. The secondsubstance 1432 may be a liquid or another fluid.

At 2124, a proximal stopper member 1434 is disposed in the interior 1412of the cartridge 1410′ as shown in FIG. 22I. The proximal stopper member1434 may be inserted by a user (e.g., using a tool) or by a mechanicaldevice (e.g., robot). The proximal stopper member 1434 closes theproximal chambers 1416 defined by the cartridge 1410′ and the distalstopper member 1414. The proximal stopper member 1434 may be positionedover an open proximal end of the cartridge 1410′ to facilitate insertionof the proximal stopper member 1434 into the body interior 1412. Theproximal stopper member 1438 may be inserted using a pressuredifferential or a small tube as described above.

In an optional step shown in FIG. 22J, a finger flange 1436 and aplunger member 1438 are coupled to the cartridge 1410′. The fingerflange 1436 may be coupled to the cartridge 1410′ such that it isprevented from moving along a longitudinal axis of the body 1410 (e.g.,using an adhesive). The plunger member 1438 may be coupled to thecartridge 1410′ such that it is movable along a longitudinal axis of thebody 1410. A distal end of the plunger member 1438 is also coupled tothe proximal stopper member 1434 (e.g., using a threaded screw), suchthat movement of the plunger member 1438 relative to the cartridge 1410′moves the proximal stopper member 1434. The finger flange 1436 and aplunger member 1438 may be coupled to the cartridge 1410′ by a user(e.g., using a tool) or by a mechanical device (e.g., robot).

Further details regarding the cartridge 1410′, the proximal and distalstopper members 1414, 1434, the needle hub assembly 1422′, the fingerflange 1436, and the plunger member 1438 are described in U.S. Utilitypatent application Ser. No. 15/801,259, which was previouslyincorporated by reference herein. The method 2100 ofmanufacturing/assembling a multiple chamber safe injection systemdepicted in FIG. 21 may take place, fully or partially, in a vacuum(e.g., vacuum chamber or vacuum room). The cartridge 1410′, the proximaland distal stopper members 1414, 1434, the needle hub assembly 1422′,the finger flange 1436, and the plunger member 1438 may bepre-sterilized before assembly.

While a single multiple chamber safe injection system ismanufactured/assembled in the method 2100 depicted in FIGS. 21 and 22Ato 22J, the same method 2100 may be used to manufacture/assemble aplurality of multiple chamber safe injection systems either in parallelor in series. While the method 2100 depicted in FIGS. 21 and 22A to 22Jinvolves a dual chamber system with two stopper members 1414, 1434, insome embodiments, a third stopper member may be added to the multiplechamber safe injection system to define a third chamber using stepssimilar to those in 2122 and 2124 described above. In some embodiments,more than three stopper members and chambers may be formed in a multiplechamber safe injection system.

Cartridge Fill Distal Chamber from Back, Pierce Then Fill

FIG. 25 depicts a rack 1210′ containing a plurality of cartridges 1410′and coupled to a plurality of needle hub assemblies 1422′ and stored ina container 1212. The rack 1210′ and the container 1212 are made frommaterials that are sterilizable. The container 1212 is closable with aseal 1214 (see FIG. 12B) to maintain the sterility of the rack 1210′ andcartridges 1410′ and needle hub assemblies 1422′ contained therein. Therack 1210′ is removed from the container 1212 and one cartridge 1410′coupled to a needle hub assembly 1422′ is removed from the rack 1210′.The rack 1210′ has a plurality of features (e.g., sleeves and/orflanges) 1216′ to hold the cartridges 1410′ and needle hub assemblies1422′ with the distal end of the cartridge 1410′ is pointed in agenerally downward direction (see FIG. 27A).

FIG. 26 depicts a method 2600 for manufacturing/assembling a multiplechamber safe injection system according to some embodiments.Corresponding partially assembled components are depicted in FIGS. 27Ato 27G. The cartridge 1410′, the proximal and distal stopper members1414, 1434, the needle hub assembly 1422′, cartridge cap 1440, thefinger flange 1436, and the plunger member 1438 may be the same systemcomponents depicted in FIGS. 22A to 24B and described above.

At 2610, a cartridge cap 1440 and a needle hub assembly 1422′ arecoupled to the distal end of the cartridge 1410′ as shown in FIG. 27A.First, the cartridge cap 1440 may be coupled to the distal end of thecartridge 1410′ by a user (e.g., using a tool) or by a mechanical device(e.g., robot). Exemplary cartridge caps 1440 are shown in FIGS. 23A and23B, and described above. The cartridge cap 1440 may be coupled to thedistal end of the cartridge 1410′ by crimping the crimp seal 1442 aroundand enlarged portion of the cartridge 1410′ at a distal end thereof.This step may be performed at the time of filling or may be performedprevious to filling and provided pre-sterilized to the filling machine.

Next, the needle hub assembly 1422′ is coupled to the distal end of thecartridge 1410′ on top of the cartridge cap 1440 as shown in FIG. 27A.As shown in FIG. 22F, the needle hub assembly 1422′ includes a needle1424 having a needle proximal end 1426. While a cartridge cap 1440 isincluded in the embodiment depicted in FIG. 27A, the cartridge cap 1440is optional and the needle hub assembly 1422′ is directly coupled to thedistal end of the cartridge 1410′ in some embodiments (compare FIGS. 24A(no cap) and 24B (with cap)). The coupling of the needle hub assembly1422′ to the cartridge 1410′ may be performed at the time of filling orthe coupling may be performed previous to filling and a pre-sterilizedcoupled system is provided to the filling machine.

At 2612, the cartridge 1410′ coupled to the needle hub assembly 1422′ isdisposed in a rack with the cartridge 1410′ pointed downward as shown inFIGS. 25 and 27A. The cartridge 1410′ may be disposed in the rack by auser (e.g., using a tool) or by a mechanical device (e.g., robot).

At 2614, a first substance 1420 is introduced into the distal chamber1418 through the open proximal end of the cartridge 1410′ as shown inFIG. 27B. The first substance 1420 may be introduced directly throughthe opening at the proximal end of the cartridge 1410′. The firstsubstance 1420 may be a liquid, a solid (e.g., compressed powder),and/or a powder. In some embodiments where the first substance 1420 is aliquid, the first substance 1420 may be lyophilized in an optional stepto form a powder as shown in FIG. 27C.

At 2616, a distal stopper member 1414 is disposed in an interior 1412 ofthe cartridge 1410′ as shown in FIGS. 27C and 27D. The distal stoppermember 1414 may be inserted by a user (e.g., using a tool) or by amechanical device (e.g., robot). The distal stopper member 1414 and thecartridge 1410′ define proximal and distal chambers 1416, 1418 in thebody interior 1412. The distal stopper member 1414 may be positionedover an open proximal end of the cartridge 1410′ to facilitate insertionof the distal stopper member 1414 into the body interior 1412 as shownin FIG. 27C.

The needle proximal end 1426 interferes with the distal stopper member1414 to temporarily prevent distal movement of the distal stopper member1414 relative to the cartridge 1410′. Components of the distal stoppermember 1414 that interfere with the needle proximal end 1426 aredepicted in FIGS. 15A to 15D and 16 to 16A, and described above.

At 2618, a second substance 1432 is introduced into the proximal chamber1416 through the open proximal end of the cartridge 1410′ as shown inFIG. 27E. The second substance 1432 may be introduced directly throughthe opening at the proximal end of the cartridge 1410′. The secondsubstance 1432 may be a liquid or another fluid.

At 2620, a proximal stopper member 1434 is disposed in the interior 1412of the cartridge 1410′ as shown in FIG. 27F. The proximal stopper member1434 may be inserted by a user (e.g., using a tool) or by a mechanicaldevice (e.g., robot). The proximal stopper member 1434 closes theproximal chambers 1416 defined by the cartridge 1410′ and the distalstopper member 1414. The proximal stopper member 1434 may be positionedover an open proximal end of the cartridge 1410′ to facilitate insertionof the proximal stopper member 1434 into the body interior 1412. Theproximal stopper member 1438 may be inserted using a pressuredifferential or a small tube as described above.

In an optional step shown in FIG. 27G, a finger flange 1436 and aplunger member 1438 are coupled to the cartridge 1410′. The fingerflange 1436 may be coupled to the cartridge 1410′ such that it isprevented from moving along a longitudinal axis of the body 1410 (e.g.,by snapping over a glass flange at the proximal end of the body 1410).The plunger member 1438 may be coupled to the cartridge 1410′ such thatit is movable along a longitudinal axis of the body 1410. A distal endof the plunger member 1438 is also coupled to the proximal stoppermember 1434 (e.g., using a threaded screw), such that movement of theplunger member 1438 relative to the cartridge 1410′ moves the proximalstopper member 1434. The finger flange 1436 and a plunger member 1438may be coupled to the cartridge 1410′ by a user (e.g., using a tool) orby a mechanical device (e.g., robot).

While a single multiple chamber safe injection system ismanufactured/assembled in the method 2600 depicted in FIGS. 26 and 27Ato 27G, the same method 2600 may be used to manufacture/assemble aplurality of multiple chamber safe injection systems either in parallelor in series. While the method 2600 depicted in FIGS. 26 and 27A to 27Ginvolves a dual chamber system with two stopper members 1414, 1434, insome embodiments, a third stopper member may be added to the multiplechamber safe injection system to define a third chamber using stepssimilar to those in 2618 and 2620 described above. In some embodiments,more than three stopper members and chambers may be formed in a multiplechamber safe injection system.

Cartridge Fill Distal Chamber from Back, Fill Then Pierce

FIG. 28 depicts a method 2800 for manufacturing/assembling a multiplechamber safe injection system according to some embodiments.Corresponding partially assembled components are depicted in FIGS. 29Ato 29G. The cartridge 1410′, the proximal and distal stopper members1414, 1434, the needle hub assembly 1422′, cartridge cap 1440, thefinger flange 1436, and the plunger member 1438 may be the same systemcomponents depicted in FIGS. 22A to 24B and described above.

At 2810, a cartridge cap 1440 is coupled to the distal end of thecartridge 1410′ as shown in FIG. 29A. The cartridge cap 1440 may becoupled to the distal end of the cartridge 1410′ by a user (e.g., usinga tool) or by a mechanical device (e.g., robot). Exemplary cartridgecaps 1440 are shown in FIGS. 23A and 23B, and described above. Thecartridge cap 1440 may be coupled to the distal end of the cartridge1410′ by crimping the crimp seal 1442 around and enlarge portion of thecartridge 1410′ at a distal end thereof. In some alternativeembodiments, the cartridge 1410′ may be supplied with the cartridge cap1440 coupled and both components pre-sterilized.

At 2812, the cartridge 1410′ coupled to the cartridge cap 1440 isdisposed in a rack with the cartridge 1410′ pointed downward as shown inFIGS. 20C and 29A. The cartridge 1410′ may be disposed in the rack by auser (e.g., using a tool) or by a mechanical device (e.g., robot).

At 2814, a first substance 1420 is introduced into the distal chamber1418 through the open proximal end of the cartridge 1410′ as shown inFIG. 29B. The first substance 1420 may be introduced directly throughthe opening at the proximal end of the cartridge 1410′. The firstsubstance 1420 may be a liquid, solid (e.g., compressed powder), and/ora powder. In some embodiments where the first substance 1420 is aliquid, the first substance 1420 may be lyophilized in an optional stepto form a powder as shown in FIG. 29C.

At 2816, a needle hub assembly 1422′ is coupled to the distal end of thecartridge 1410′ on top of the cartridge cap 1440 as shown in FIG. 29E.As shown in FIG. 22F, the needle hub assembly 1422′ includes a needle1424 having a needle proximal end 1426. During insertion of the needlehub assembly 1422′into the cartridge interior 1412, the needle 1424 anda needle proximal end 1426 pierce the cartridge cap 1440. The septum1444 in the cartridge cap 1440 depicted in FIGS. 23A and 23B isconfigured to be pierced by the needle proximal end 1426. In somealternative embodiments, the cartridge 1410′ may be supplied with theneedle hub assembly 1422′ coupled and both components pre-sterilized.

At 2818, a distal stopper member 1414 is disposed in an interior 1412 ofthe cartridge 1410′ as shown in FIGS. 29E and 29F. The distal stoppermember 1414 may be inserted by a user (e.g., using a tool) or by amechanical device (e.g., robot). The distal stopper member 1414 and thecartridge 1410′ define proximal and distal chambers 1416, 1418 in thebody interior 1412. The distal stopper member 1414 may be positionedover an open proximal end of the cartridge 1410′ to facilitate insertionof the distal stopper member 1414 into the body interior 1412. Thedistal stopper member 1414 may be inserted using a pressure differentialor a small tube as described above.

The needle proximal end 1426 interferes with the distal stopper member1414 to temporarily prevent distal movement of the distal stopper member1414 relative to the cartridge 1410′. Components of the distal stoppermember 1414 that interfere with the needle proximal end 1426 aredepicted in FIGS. 15A to 15D and 16 to 16A, and described above.

At 2820, a second substance 1432 is introduced into the proximal chamber1416 through the open proximal end of the cartridge 1410′ as shown inFIG. 29G. The second substance 1432 may be introduced directly throughthe opening at the proximal end of the cartridge 1410′. The secondsubstance 1432 may be a liquid or another fluid.

At 2822, a proximal stopper member 1434 is disposed in the interior 1412of the cartridge 1410′ as shown in FIG. 29H. The proximal stopper member1434 may be inserted by a user (e.g., using a tool) or by a mechanicaldevice (e.g., robot). The proximal stopper member 1434 closes theproximal chambers 1416 defined by the cartridge 1410′ and the distalstopper member 1414. The proximal stopper member 1434 may be positionedover an open proximal end of the cartridge 1410′ to facilitate insertionof the proximal stopper member 1434 into the body interior 1412. Theproximal stopper member 1438 may be inserted using a pressuredifferential or a small tube as described above.

In an optional step (not shown), a finger flange and a plunger memberare coupled to the cartridge 1410′. The finger flange may be coupled tothe cartridge 1410′ such that it is prevented from moving along alongitudinal axis of the body 1410 (e.g., by snapping over a glassflange at the proximal end of the body 1410). The plunger member may becoupled to the cartridge 1410′ such that it is movable along alongitudinal axis of the body 1410. A distal end of the plunger memberis also coupled to the proximal stopper member 1434 (e.g., using athreaded screw), such that movement of the plunger member relative tothe cartridge 1410′ moves the proximal stopper member 1434. The fingerflange and a plunger member may be coupled to the cartridge 1410′ by auser (e.g., using a tool) or by a mechanical device (e.g., robot).

While a single multiple chamber safe injection system ismanufactured/assembled in the method 2800 depicted in FIGS. 28 and 29Ato 29G, the same method 2800 may be used to manufacture/assemble aplurality of multiple chamber safe injection systems either in parallelor in series. While the method 2800 depicted in FIGS. 28 and 29A to 29Ginvolves a dual chamber system with two stopper members 1414, 1434, insome embodiments, a third stopper member may be added to the multiplechamber safe injection system to define a third chamber using stepssimilar to those in 2818 and 2820 described above. In some embodiments,more than three stopper members and chambers may be formed in a multiplechamber safe injection system.

FIG. 30 depicts a cartridge stopper 1446 according to some embodiments.The cartridge stopper 1446 can be made from a soft polymer such that itis pierceable by the needle proximal end 1426. Further, the cartridgestopper 1446 includes a vent 1448 for lyophilization of liquids in thecartridge interior 1412.

Autoinjector System Single Chamber

FIGS. 31A to 31H depict an auto injector system 3100 including adisposable injection system/syringe 3110 and a reusable drive system3150 according to some embodiments. The autoinjector system 3100 allowsuse of injection system/syringes 3110 that are readily available in aclinical setting without having to add items to a supply chain. Theautoinjector system 3100 also includes a safety function to minimizeexposure of a sharp needle as described below. These and otheradvantages of the autoinjector system 3100 are explained below.

As shown in FIG. 31A, the disposable injection system/syringe 3110includes an injection system/syringe body 3112, a stopper member 3114, aplunger member 3116, a finger flange 3118, a needle hub assembly 3120, arigid needle shield 3122, and a pull ring 3124 to facilitate removal ofthe rigid needle shield 3122 from the needle hub assembly 3120. Theinjection system/syringe 3110 may be a safe injection system thatretracts the sharp needle at least into the injection system/syringebody 3112 to minimize the risk of a needle stick. Examples of such safeinjection systems are described in U.S. Utility patent application Ser.No. 14/696,342, which was previously incorporated by reference herein.The reusable drive system 3150 includes a drive system body 3152, aplunger actuator/pusher 3154, a flange holder/carriage 3156, and acollar 3164.

When the injection system/syringe 3110 is mounted in the drive system3150, as shown in FIG. 31B, the plunger actuator/pusher 3154 isconfigured to move the plunger member 3116 distally relative to theinjection system/syringe body 3112. The flange holder/carriage 3156 isconfigured to move the injection system 3110 distally and/or proximallyrelative to the drive system body 3152. The plunger actuator/pusher 3154and the flange holder/carriage 3156 are in their respective fullproximal positions in FIGS. 31A and 31B. In this position, the collar3164 of the drive system 3150 prevents the sharp needle of the injectionsystem/syringe 3110 from contacting a user's skin. In addition, in FIG.31B, the rigid needle shield 3122 prevents the needle from contacting auser's skin.

FIG. 31C shows the autoinjector system 3100 in a closed configuration(versus the open configuration in FIGS. 31A and 31 B). In the closeconfiguration, various user interface components of the drive system3150 are visible. The drive system 3150 includes a display 3158, abutton 3160, and the light ring 3162 around the button 3160. In thesystem configuration depicted in FIG. 31C, the display 3158 renders anindication of the size of the injection systems/syringe (e.g., 1.0 ml).The button 3160 allows a user to provide input to the autoinjectorsystem 3100. The light ring 3162 can change colors to indicate varioussteps in the injection process. As shown in FIG. 31C, the pull ring 3124is accessible at the distal end of the drive system 3150 because itextends distally beyond the collar 3164.

The top half of the drive system 3150 has been cut away from FIGS. 31Dto 31G to visualize various components of the autoinjector system 3100during injection with the drive system 3150 in a closed configuration.

In FIGS. 31D, the rigid needle shield 3122 has been removed from theneedle hub assembly 3120. In some embodiments, the autoinjector system3100 renders an instruction on the display 3158 for the user to pull onthe pull ring 3124 to remove the rigid needle shield 3122 from theneedle hub assembly 3120. In some embodiments, the autoinjector 3100includes components that grasp the rigid needle shield 3122 (e.g., oneor more arms) while the flange holder/carriage 3156 moves the injectionsystem/syringe 3110 (e.g., from a distal position to a proximalposition) to separate the rigid needle shield 3122 from the needle hubassembly 3120. In such embodiments, the user would only have to removethe separated rigid needle shield 3122 from the auto injection system3100. The collar 3164 prevents exposure of the needle 3126 to a user.

In FIG. 31E, the flange holder/carriage 3156 has moved the injectionsystem/syringe 3110 distally. At the same time, the plungeractuator/pusher 3154 has moved the same distance distally to maintaincontact with the thumb pad at the proximal end of the plunger member3116. Moving the injection system/syringe 3110 distally extends theneedle 3126 distally beyond the collar 3164, thereby exposing the needle3126 for injection. Before the flange holder/carriage 3156 moves theinjection system/syringe 3110 distally, the autoinjector system 3100 mayrender an instruction on the display 3158 for the user to press theautoinjector against an injection site. In such embodiments, moving theinjection system/syringe 3110 distally may puncture the injection site.

In FIG. 31F, the plunger actuator/pusher 3154 has moved to its fulldistal position. This movement drives the plunger member 3116 and thestopper member 3114 attached thereto distally to eject a medicine fromthe injection systems/syringe 3110 through the needle 3126 and into thepatient.

In FIG. 31G, movement of the plunger member 3116 and the stopper member3114 two and end of injection position has caused the needle 3126 to beretracted into the injection systems/syringe body 3112 as described U.S.Utility patent application Ser. No. 14/696,342, which was previouslyIncorporated by reference herein. Retraction of the needle 3126 rendersthe injection systems/syringe 3110 safe for removal from the drivesystem 3150 as shown in FIG. 31H. After the used injectionsystem/syringe 3110 has been removed, a new injection system/syringe3110 can be loaded into the drive system 3150 to ready the auto injectorsystem 3100 ready for another injection.

The drive system 3150 also includes a first motor to move the plungeractuator/pusher 3154, a second motor to move the flange holder/carriage3156, a controller operatively coupled to the first and second motors,and one or more sensors operatively coupled to the controller. Thesensors may include one or more of an accelerometer, a contact sensor, aposition sensor, a gyroscope, a thermometer, and a skin contact sensor.In some embodiments, the sensor is a skin contact sensor, and thecontroller injects the medicine only when the skin contact sensorconfirms contact between the autoinjector system 3100 and a patient.

Dual Chamber

FIGS. 32A to 32J depict an autoinjector system 3200 configured for usewith a multiple chamber injection system 3210. The drive system 3250depicted in FIGS. 32A to 32J is similar to the drive system 3150depicted in FIGS. 31A to 31H. In fact, drive systems 3150, 3250 may bethe same drive system with altered programming.

As shown in FIG. 32A, the disposable injection system/syringe 3210includes an injection system/syringe body 3212, first and second stoppermembers 3228, 3214, a plunger member 3216, a finger flange 3218, aneedle hub assembly 3220, and a rigid needle shield 3222. The injectionsystem/syringe 3210 may be a safe injection system that retracts thesharp needle at least into the injection system/syringe body 3212 tominimize the risk of a needle stick. Examples of such safe injectionsystems are described in U.S. Utility patent application Ser. No.15/801,259, which was previously incorporated by reference herein. Thereusable drive system 3250 includes a drive system body 3252, a plungeractuator/pusher 3254, a flange holder/carriage 3256, and a collar 3264.

When the injection system/syringe 3210 is mounted in the drive system3250, as shown in FIG. 32B, the plunger actuator/pusher 3254 isconfigured to move the plunger member 3216 distally relative to theinjection system/syringe body 3212. The flange holder/carriage 3256 isconfigured to move the injection system 3210 distally and/or proximallyrelative to the drive system body 3252. The plunger actuator/pusher 3254and the flange holder/carriage 3256 are in their respective fullproximal positions in FIGS. 32A and 32B. In this position, the collar3264 of the drive system 3250 prevents the sharp needle of the injectionsystem/syringe 3210 from contacting a user's skin. In addition, in FIG.32B, the rigid needle shield 3222 prevents the needle from contacting auser's skin.

FIG. 32C shows the autoinjector system 3200 in a closed configuration(versus the open configuration in FIGS. 32A and 32B). In the closeconfiguration, various user interface components of the drive system3250 are visible. The drive system 3250 includes a display 3258, abutton 3260, and the light ring 3262 around the button 3260. In thesystem configuration depicted in FIG. 32C, the display 3258 renders anindication of the size of the injection systems/syringe (e.g., 1.0 ml).The button 3260 allows a user to provide input to the autoinjectorsystem 3200. The light ring 3262 can change colors to indicate varioussteps in the injection process. As shown in FIG. 32C, the rigid needleshield 3222 is not easily accessible at the distal end of the drivesystem 3250 because it barely extends distally beyond the collar 3264.

FIGS. 32D to 32J depict various steps in a method of mixing andinjecting medicines using the autoinjector system 3200 according to someembodiments. In FIG. 32D, the display 3258 is rendering a messageinstructing a user to push the button 3262 mix a medicine with adiluent. This message can be accompanied by the light ring 3262 turninggreen to signal go. When the user presses the button 3262, the plungeractuator/pusher 3254 moves distally to transfer diluent from a proximalchamber to a distal chamber as shown in FIG. 7G to 7J. In FIG. 32E, thedisplay 3250 is rendering a message instructing a user to shake theautoinjector system 3202 mix the medicine with the diluent.

In FIG. 32F, the display 3250 is rendering a message instructing a userto point the autoinjector system 3200 upward and will move the rigidneedle shield 3222. As shown in FIG. 32G, when a position sensor in theautoinjector system 3200 detects that the system 3200 is pointed upward,the flange holder/carriage 3256 moves the injection systems/syringe 3210distally to extend the rigid needle shield 3222 for removal. Removingthe rigid needle shield 3222 only when the system 3200 is pointed upwardprevents accidental expulsion of medicine due to pressure buildup fromfluid transfer and mixing.

In some embodiments, the user is expected to pull on the rigid needleshield 3222 to remove it from the needle hub assembly 3220. In someembodiments, the autoinjector 3200 includes components that grasp therigid needle shield 3222 (e.g., one or more arms) while the flangeholder/carriage 3256 moves the injection system/syringe 3210 (e.g., froma distal position to a proximal position) to separate the rigid needleshield 3222 from the needle hub assembly 3220. In such embodiments, theuser would only have to remove the separated rigid needle shield 3222from the auto injection system 3200. The collar 3264 prevents exposureof the needle 3226 to a user as shown in FIG. 32H.

In FIG. 32F, the display 3250 is rendering a message instructing a userto place the autoinjector system 3200 on user's thigh and to press thebutton 3260 to give the injection. In some embodiments, a skin contactsensor prevents injection until contact between the autoinjector system3200 and the user is detected. Detection of contact and readiness forinjection can be indicated using the light ring 3262 (e.g., a green ringfor go). When the user presses the button 3260 for injection, the flangeholder/carriage 3256 moves the injection systems/syringe 3210 distallyto insert the needle into the patient, and the plunger actuator/pusher3254 moves distally to complete the injection as shown in FIGS. 7K to7P.

After the injection is completed, the display 3250 renders a messageconfirming the injection and instructing a user to remove and dispose ofthe spent syringe. A new injection system/syringe 3210 can be loadedinto the drive system 3252 prepare the autoinjector system 3200 foranother injection.

Multiple Chamber Safe Injection System with Luer Connector

FIGS. 33 to 40 depict a multiple chamber safe injection system 3300 witha luer connector 3310. As shown in FIGS. 33 and 34 , the luer connector3310 is a standard connector that facilitates use of the system 3300with a wide variety of needles and tubing. The system 3300 includes astandard luer cap 3312 that seals the luer connector 3310 during mixingof the drug components before delivery/injection.

In some embodiments, the drug components include a drug solvent 3314 ina proximal chamber and a drug powder and/or solid (e.g., compressedpowder) 3316 and a distal chamber. The drug solvent 3314 can betransferred from the proximal chamber to the distal chamber to mix withthe drug powder and/or solid 3316 via a transfer pipe 3318 with variousopenings. The distal end of the transfer pipe 3318 is coupleable via theLuer connector 3310 with a wide variety of needles and tubing. Thefinger flange and a plunger member also include aratcheting/anti-retraction system 3320 to limit motion of the plungermember during mixing to the distal direction.

FIG. 35 depicts a transfer pipe 3318 for use with the multiple chambersafe injection system 3300 according to some embodiments. The proximalend of the transfer pipe 3318 includes a piercing tip 3322 configured topierce the distal stopper member to allow the drug diluent 3314 totransfer from the proximal chamber to the distal chamber to mix with thedrug powder and/or solid 3316. The next feature distally along thetransfer pipe 3318 is a liquid entrance slot 3324 configured to allowthe drug diluent 3314 to enter from the proximal chamber. The nextfeature is a liquid exit opening 3326 configured to allow the drugdiluent 3314 to exit to the distal chamber. The liquid entrance slot3324 and the liquid exit opening 3326 are configured such that they spanthe distal stopper member to maximize liquid transfer. The next featureis a blocking rod 3328 to prevent the drug diluent 3314 from exiting outthe distal end of the transfer pipe 3318. The next feature is a washer3330 configured to provide a reactive force to allow the piercing tip3322 to pierce the distal stopper member. The next feature is an exitslot 3332 configured to allow the mixed drug to enter the distal end ofthe transfer pipe 3318. The distal most feature is an expanded endopening 3334 configured to mate with a variety of needles and tubing viathe luer connector 3310. The expanded end opening also provides frictionwith the luer passage to hold the transfer pipe 3318 in place duringfilling of the system 3300.

FIG. 36 depicts the fluid path 3336 during transfer of the drug diluent3314 from the proximal chamber to the distal chamber. As describedabove, the fluid path 3336 goes through the liquid entrance slot 3324,travels along a proximal portion of the transfer pipe 3318, and exitsthe liquid exit opening 3326. Transfer of the drug diluent 3314 from theproximal chamber to the distal chamber increases the pressure in thedistal chamber. The ratcheting/anti-retraction system 3320 preventsunwanted proximal movement of the plunger member resulting from thebuilt-up pressure in the distal chamber. The teeth 3338 of theratcheting/anti-retraction system 3320 are only present at a distalportion of the plunger member, which interacts with tabs 3340 in thefinger flange during mixing. Even if the user releases pressure on theplunger member during transfer, the ratcheting system/anti-retraction3320 holds the plunger member in place. An alternativeratcheting/anti-retraction system is described below.

FIG. 37 depicts the fluid path 3336 at the end of the transfer of thedrug diluent 3314 from the proximal chamber to the distal chamber. Theliquid entrance slot 3324 allows the drug diluent to continue totransfer even as the proximal and distal stoppers approach each other.

FIG. 38 depicts the multiple chamber safe injection system 3300 afterthe transfer of the drug diluent 3314 is complete. Pressurized air inthe distal chamber is prevented from pushing the plunger memberproximally by the ratcheting system 3320. The user can shake the system3300 to mix the drug diluent 3314 with the drug powder and/or solid 3316in the distal chamber.

FIG. 39 depicts the multiple chamber safe injection system 3300 afterthe luer cap 3312 has been removed with the system 3300 in an upwardposition to avoid the pressure in the distal chamber interjecting any ofthe mixed drug therein. Instead pressurized air is purged from thedistal chamber. A needle 3342 with a corresponding luer connector iscoupled to the luer connector 3310 in the system 3300 to prepare thesystem 3300 for injection.

FIG. 40 depicts the multiple chamber safe injection system 3300 duringinjection. The fluid path 3344 during injection is along the outside ofthe distal end of the transfer pipe 3318 and through the needle 3342.During injection, the blocking rod 3328 prevents the mixed drug fromtraveling retrograde into the plunger member. The plunger member alsoincludes an elastomeric seal to prevent backflow. Because the plungermember has moved relative to the finger flange such that the ratchetteeth at this gauge from the tabs, the plunger member can be moved inboth a distal and a proximal direction during injection.

Vent Plug

FIGS. 41 to 47 depict a multiple chamber injection system 4100 with avent plug 4154 according to some embodiments. The vent plug 4154 isconfigured (e.g., sized and shaped) to allow air to escape the system4100 while substantially retaining liquids. As shown in FIG. 41 , thesystem 4100 includes a syringe body 4110 having a needle coupling member4156 at a distal end thereof. The needle coupling member 4156 may be afemale Luer connector. The system 4100 also includes a finger flange4136 coupled to a proximal end of the syringe body 4110 and a plungermember 4138 inserted through the finger flange 4136 and into an interiorof the syringe body 4110.

Also disposed in the interior of the syringe body 4110 are proximal anddistal stopper members 4134, 4114. The proximal and distal stoppermembers 4134, 4114 and the syringe body 4110 define a proximal chamber4116. The distal stopper member 4114 and the syringe body 4110 define adistal chamber 4118. In the embodiment depicted in FIG. 41 , the distalchamber 4118 contains a gas 4152 (e.g., air) and the proximal chamber4116 contains a liquid 4132. The system 4100 also includes a mix tube4124 configured to pierce the distal stopper member 4114 to fluidlycouple the proximal and distal chambers 4116, 4118. FIG. 41A depicts ananti-retraction mechanism 3321 (described below) for use with themultiple chamber injection system 4100 according to some embodiments.

The system 4100 further includes a cap 4150 (e.g., Luer cap) coupled tothe needle coupling member 4156 for storage of the system 4100components before use (e.g., injection). Moreover, the system 4100includes a vent plug 4154 disposed at least partially in the needlecoupling member 4156 and around a distal end of the mix tube 4124. Thevent plug 4154 is configured (sized and shaped) to allow air to escapethe system 4100 while substantially retaining liquids.

FIG. 42 depicts the system 4100 depicted in FIG. 41 after the plungermember 4138 and the proximal stopper member 4134 coupled thereto havebeen inserted distally into the interior of the syringe body 4110according to some embodiments. Before the proximal end of the mix tube4124 pierces completely through the distal stopper member 4114 (as shownin FIG. 41 ), the incompressibility of the liquid 4132 in the proximalchamber 4116 transmits distally directed force from the plunger member4138 and the proximal stopper member 4134 to the distal stopper member4114 moving the distal stopper member 4114 distally. Distal movement ofthe distal stopper member 4114 causes the proximal end of the mix tube4124 to pierce completely through the distal stopper member 4114 andfluidly couple the proximal and distal chambers 4116, 4118. Fluidlycoupling the proximal and distal chambers 4116, 4118 allows the liquid4132 to be driven from the proximal chamber 4116 to the distal chamber4118 by a distally directed force from the plunger member 4138 and theproximal stopper member 4134 as shown in FIG. 42 .

Also shown in FIG. 42 , the proximal chamber 4116 has collapsed almostcompletely, and almost all of the liquid 4132 has been driven from theproximal chamber 4116 to the distal chamber 4118. The volume of theliquid 4132 driven into the distal chamber 4118 compresses the gas 4152in the distal chamber 4118 increasing the pressure in the distal chamber4118. If this increased pressure is not vented from the distal chamber4118, it may unintentionally eject some of the liquid 4132 from thedistal chamber 4118, both wasting the liquid 4132 and reducing theaccuracy and precision of the system 4100. Before the cap 4150 isremoved from the system 4100, the increased pressure in the distalchamber 4118 may also be exerted back through the mix tube 4124, therebymoving some of the liquid 4132 back into the proximal chamber 4116 andreducing the accuracy and precision of the system 4100. The backpressure may also move the proximal stopper member 4134 and the plungermember 4138 proximally. Some multiple chamber injection systems includelatches on the plunger member to prevent proximal movement of theplunger member.

FIGS. 43A-43D depicts a method of mixing a two part injectable substance(e.g., medication) for injection according to some embodiments. Themultiple chamber injection system 4100 depicted in FIGS. 43A-43D issimilar to the multiple chamber injection system 4100 depicted in FIGS.41 and 42 and described above. One difference is that the system 4100depicted in FIGS. 43A-43D includes a dry component (e.g., lyophilizedpowder and/or solid, e.g., compressed powder) (not shown) in the distalchamber 4118 to be solubilized by the liquid 4132 to for the two partinjectable substance. In FIG. 43A, the cap 4150 is removed from theneedle coupling member 4156. In FIG. 43B, a distally directed force fromthe plunger member 4138 and the proximal stopper member 4134 causesdistal movement of the distal stopper member 4114, which in turn causesthe proximal end of the mix tube 4124 to pierce completely through thedistal stopper member 4114 and drives the liquid 4132 from the proximalchamber 4116 to the distal chamber 4118. In FIG. 43C, the system 4100 isshaken to mix the liquid 4132 in the distal chamber 4118 with the drycomponent (not shown) therein. In FIG. 43D, a needle 4166 is attachedvia a needle coupling member 4156 (e.g., male Luer connector) to preparethe system 4100 for injection. Without a venting/liquid restrictingcomponent, during the mixing in FIG. 43C, the increased pressure in thedistal chamber 4118 may eject some of the liquid 4132 (and thesolubilized dry component), reducing the accuracy and precision of thesystem 4100.

FIG. 44 is a detailed view of the distal end of the syringe body 4110,including a vent plug 4154 which is disposed at least partially in theneedle coupling member 4156 and around a distal end of the mix tube 4124according to some embodiments. FIG. 45 is an even more detailed view ofthe distal end of the syringe body 4110, including the vent plug 4154according to some embodiments. FIG. 45 shows that the vent plug includesa plurality of channels 4158, which are configured (e.g., sized andshaped) to allow gases (e.g., air) to escape 4160 the interior of thesyringe body 4110 (e.g., distal chamber 4118 see FIG. 44 ), whilepreventing liquids from escaping the interior of the syringe body 4110.

FIG. 46 is a detailed view of a vent plug 4154 for use in a multiplechamber injection system 4100 according to some embodiments. Manycomponents of the system 4100 are omitted for clarity. The vent plug4154 is disposed around a mix tube 4124 and includes a plurality ofchannels 4158. FIG. 47 is a detailed view of a vent plug 4154 for use ina multiple chamber injection system 4100 according to some embodiments.FIG. 47 depicts the center opening 4162 of the vent plug 4154 throughwhich a mix tube 4124 may be inserted. FIG. 47 also depicts a pluralityof channels 4158 that may be molded into an interior surface of the ventplug 4154. The plurality of channels 4158 are configured (e.g., sizedand shaped) to allow gases to escape/vent from the interior of thesyringe body 4110 while preventing liquids from escaping the interior ofthe syringe body 4110. Venting gases and releasing pressure from theinterior of the syringe body 4110 minimizes unintended ejection ofliquid from the interior of the syringe body 4110 and increases accuracyand precision of the system 4100. Venting gases and releasing pressurefrom the interior of the syringe body 4110 also minimizes unintendedproximal movement of the plunger member 4138 from back pressure, therebyeliminating the need for latches on the plunger member 4138 to preventproximal movement thereof.

FIG. 48 depicts an alternative embodiment of the vent plug 4154 wherethe vent channels 4158 are present in an exterior surface of the ventplug 4154. The vent plug 4154 is configured to be installed into thedistal needle interface 4156 (see FIG. 45 ), where the vent channels4158 are in contact with the interior surface of the distal needleinterface 4156, maintaining the open vent channel 4158 to an exterior ofthe syringe body 4110. The vent channels 4184 may be linear or may benon-linear with bends and turns along the longitudinal axis of the ventplug 4154 (as shown in FIG. 48 ). FIG. 48 illustrates vent channels 4184that are non-linear, creating a tortuous path for fluid flow along thelongitudinal axis of the vent plug 4154. As fluid is forced through thevent channels 4158, bends or corners in the vent channels 4158 provideimpediments/resistance to fluid flow. These impediments are configuredto take advantage of fluid frictional effects such that more viscousfluids (e.g., liquids) require higher pressure to flow through the ventchannels 4158. For example, gases (e.g., air) will flow through thesevent channels 4158 at a predetermined pressure generated in the syringebody 4110. Liquids (e.g., water or liquid drugs) require a higherpressure to flow through the vent channels 4158. This pressuredifferential requirement for fluid flow provides a restriction toprevent water or liquid drug from being unintentionally expelled fromthe end of the syringe body 4110 during mixing (see FIG. 43C) when thesyringe cap 4150 is removed. The pressure for fluid flow may also begenerated by shaking the syringe during mixing, such as g-forces fromshaking applied over the surface of the liquid. The vent channels 4158are configured such that high g-forces resulting from shaking thesyringe during mixing do not apply a large enough force on the liquid toexpel the liquid during shaking. The vent channels 4158 may beconstructed to provide orifices for fluid flow, capillary channels,and/or high fluid friction surfaces to tailor the flow restriction fordifferent fluids. This embodiment also depicts a central opening 4164 ofthe vent plug 4154 through which a mix tube 4124 may be inserted. Thecentral opening 4164 may be disposed entirely through the vent plug ormay be a blind hole with a bottom for locating the distal end of the mixtube 4124.

Alternative Ratcheting/Anti-Retraction System

An alternative embodiment of the ratcheting/anti-retraction system isillustrated in FIG. 41, 41A and 49-56 . As shown in FIGS. 41 and 49 ,this ratcheting/anti-retraction system is configured for use with aplunger member 4138, 3516 having a smooth exterior. An anti-retractionfeature 3321, 4090 (see

FIGS. 41A and 42 ) includes at least one brake tab 3321-1, 4092. Thebrake tab 3321-1, 4092 may be constructed from sheet metal, or a polymermaterial. Sheet metal brake tab 3321-1, 4092 may be configured to havesharp edges on the plunger member engaging surfaces 3329 which enablethe brake tab 3321-1, 4092 to deform the exterior surface of the plungermember 4138, 3516. The anti-retraction feature 3321, 4090 andintercoupled brake tabs 3321-1, 4092 may be configured to elasticallydeform upon insertion of the plunger member 4138, 3516 through theanti-retraction feature 3321, 4090, deflecting the brake tabs 3321-1,4092. The elasticity of the brake tabs 3321-1, 4092 provides a biasingforce which ensures there is contact between the plunger member engagingsurfaces 3329 and the exterior of the plunger member 4138, 3516.

The anti-retraction feature 3321, 4090 is inserted into a transverseslot 3323, 3584 in the finger flange 4136, 3580 with the brake tabs3321-1, 4092 bent distally 3325. Pre-bending the brake tabs 3321-1, 4092allows the brake tabs 3321-1, 4092 to flex distally upon insertion ofthe plunger member 4138, 3516 into the finger flange 4136, 3580, whilepreventing movement of the plunger member 4138, 3516 in a proximaldirection. The amount of pre-bend may be between approximately 10degrees and approximately 80 degrees, preferably 45 degrees per braketab 3321-1, 4092. Alternatively, the brake tab 3321-1, 4092 may be flatwhen inserted into the transverse slot 3323, 3584, and may be bent uponinsertion of the plunger member 4138, 3516 into the finger flange 4136,3580. Bearing surfaces/fit tabs 3321-2, 3596, 4096 on theanti-retraction feature 3321, 4090 are configured to engage the interiorsurfaces of the finger flange 4136, 3580 defining the transverse slot3323, 3584 to react the forces applied to the brake tab 3321-1, 4092from insertion of the plunger member 4138, 3516. The anti-retractionfeature 3321, 4090 may have retention barbs/tabs 3327, 3594, 4094 tohold the anti-retraction feature 3321, 4090 in the transverse slot 3323,3584 in the finger flange 4136, 3580. While the ratcheting systemsherein are depicted and described for use with a dual chamber syringethe ratcheting systems may be used with any syringe or cartridgeinjection system where it is desired to prevent movement of the plungermember in the proximal direction.

FIGS. 49 to 56 depict the addition of a one-way ratchet to the dualchamber injection systems described herein (and in the other patentapplications incorporated by reference herein). The one-way ratchetenables the plunger member to be moved distally with minimal drag forceand prevents the plunger member from moving proximally by the engagementof ratchet teeth onto the outer surface of the plunger member. Duringthe mixing phase of the multi-component injectable preparation airpressure accumulates in the distal chamber as the liquid is transferred.This pressure builds and produces a proximally directed reaction forceon the user's thumb. The addition of a toothless ratchet counteractsthis reaction force, preventing the plunger member from movingproximally. With the toothless ratchet engaged, the user does not needto continually apply a distally directed force to maintain plungermember position. The ratchet may be toothless, where the plunger memberis smooth on the outside surface and the ratchet arms are configured todig into the plunger member. In this case the position of the plungermember is maintained in infinitely small increments. Alternatively, theratchet may engage with annular grooves in or threads on the outsidesurface of the plunger member, providing an incremental position stop.The annular grooves may provide a tactile and/or audible click orfeedback to the user that the ratchet is engaged.

FIG. 49 depicts a dual chamber injection system 3500 with a fingerflange 3580 having an anti-retraction feature 3590 according to someembodiments. The anti-retraction feature 3590 prevents proximal movementof the plunger member 3516 relative to the syringe body 3510, whileallowing distal movement. In addition to the syringe body 3510, theplunger member 3516, the finger flange 3580, and the anti-retractionfeature 3590, the dual chamber injection system 3500 also includesproximal and distal stopper members 3512, 3514, and a needle hubassembly 3570. The injection system 3500 depicted in FIG. 49 may alsoinclude a needle assembly 3530 which has a proximal and distal end. Theproximal end is configured to have fluid passages (not shown, but seeFIG. 35 (3324), FIG. 9C (885), and/or FIG. 7E (270)) for transferringfluid from the proximal chamber 3522 to the distal chamber 3524 when theplunger member 3516 is moved distally. The plunger member 3516 isinserted into an interior 3518 of the syringe body 3510 via a proximalopening in the syringe body. The proximal and distal stopper members3512, 3514 together with the syringe body 3510 define a proximal drugchamber 3522. The distal stopper member 3514 and the syringe body 3510define a distal drug chamber 3524. The plunger member 3516 may bemanually manipulated to insert the proximal stopper member 3512 relativeto the syringe body 3510. If a non-compressible fluid is disposed in theproximal drug chamber 3522, inserting the proximal stopper member 3512also inserts the distal stopper member 3514 relative to the syringe body3510.

FIGS. 50 to 53 depict the finger flange 3580, which is configured to bemounted onto a small flange 3511 formed at the proximal end of thesyringe body 3510 (see FIG. 53 ). As shown in FIG. 50 , the fingerflange 3580 defines a first recess 3582 configured to receive the smallflange 3511 to couple the finger flange 3580 to the syringe body 3510.The finger flange 3580 also defines a second recess 3584 configured toreceive the anti-retraction mechanism 3590. The anti-retractionmechanism 3590 includes a pair of brake tabs 3592 configured to providean opposing force with proximal movement of the plunger member 3516relative to the anti-retraction mechanism 3590, while allowing distalmovement. The opposing force may include a frictional force as the braketabs 3592 contact an outer surface 3517 of the plunger member 3516 and areaction force as the brake tabs 3592 dig into an outer surface 3517 ofthe plunger member 3516. The acute angle of the brake tabs 3592 createsthe reaction force parallel to the plunger member 3516, exerted by asharp curved edge of each of the brake tabs 3592 contacting the surface3517 of the plunger member 3516. This reaction force along with thefrictional force prevents the plunger member 3516 from moving in theproximal direction. The finger flange 3580 further defines a “C” shapedopening 3586 configured to receive the plunger member 3516 (see FIG. 50). Due to the “C” shaped opening 3586, the finger flange 3580 can beslid onto the small flange 3511 from the side of the small flange 3511after the plunger member 3516 is inserted during assembly. The “C”shaped finger flange 3580 and anti-retraction mechanism 3590 depicted inFIGS. 49 to 53 can be slid/snapped on to the small flange 3511 of thesyringe body 3510 after the plunger member 3516 is inserted. Syringebodies 3510 with plunger members 3516 screwed into proximal stoppermembers 3514 are able to pack more tightly into shipping trays fortransportation. The finger flange 3580 with is the anti-retractionmechanism 3590 is snapped after shipping, and snaps around both thesyringe body 3510 and the plunger member 3516.

As shown in FIG. 51 , the anti-retraction mechanism 3590 is a generally“C” shaped clip. In some embodiments, the anti-retraction mechanism 3590is cut or stamped from a sheet of metal and then certain portionsthereof are bent to the final shape. The anti-retraction mechanism 3590includes a pair of brake tabs 3592 configured to provide an opposingfrictional force with proximal movement of the plunger member 3516 asdescribed above. The brake tabs 3592 are the elastically deformable andself-energizing. The brake tabs 3592 extend at an acute angle in adistal direction relative to the plane of the anti-retraction mechanism3590 (i.e., the brake tabs 3592 are bent downwards). The angle andelasticity of the brake tabs 3592 allows the plunger member 3516 toslide past the break tabs 3592 in the in distal direction. When theplunger member 3516 is pulled in a proximal direction relative to thebrake tabs 3592, the brake tabs 3592 make contact with and dig into anouter surface 3517 of the plunger member 3516 and prevent proximalplunger member 3516 movement relative to the break tabs 3592. Becausethe brake tabs 3592 are self-energizing, with attempted proximalmovement, the brake tabs 3592 engages with the plunger member 3516 byincreasing a frictional force applied to the plunger member 3516 and anamount of digging into the plunger member 3516 to prevent its proximalmovement. In effect, the brake tabs 3592 form a pair of pawls to engagethe plunger member 3516 and prevent proximal movement thereof. In someembodiments, the plunger member (not shown) may have annular groovesthreads and/or formed thereon to increase the ratcheting effect of thebrake tabs 3592. The anti-retraction mechanism 3590 and the brake tabs3592 prevent removal of the plunger member 3516 from the dual chamberinjection system 3500 after use.

The anti-retraction mechanism 3590 also includes a pair of retentiontabs 3594 configured to hold the anti-retraction mechanism 3590 in thesecond recess 3584 of the finger flange 3580. The retention tabs 3594are bent inward so that they are configured to grip the inside of thesecond recess 3584 in the finger flange 3580 with a frictional force anda reaction force to prevent removal of the anti-retraction mechanism3590 from the second recess 3584. The retention tabs 3594 are alsoself-energizing to provide increasing frictional and reaction force asthe anti-retraction mechanism 3590 is pulled from the second recess3584. In the embodiment depicted in FIG. 52 , the finger flange 3580includes a pair of openings 3588 configured to receive the retentiontabs 3594 from the anti-retraction mechanism 3590 to retain theanti-retraction mechanism 3590 in the second recess 3584 by interferenceinstead of friction.

As shown in FIG. 51 , the anti-retraction mechanism 3590 also includesfour fit tabs 3596 configured to reduce a tolerance between the secondrecess 3584 and the anti-retraction mechanism 3590 thereby providing atighter fit of the anti-retraction mechanism 3590 in the second recess3584. The original tolerance is larger because, in some embodiments, thefinger flange 3580 is molded from a polymer, and therefore has minimumsize limitations for recesses that can be accurately and preciselyformed therein. On the other hand, the anti-retraction mechanism 3590 iscut from a sheet of metal, and therefore has a thinner profile then theheight of the second recess 3584. The fit tabs 3596 increase thethickness/height of the anti-retraction mechanism 3590, therebyproviding a tighter fit in the second recess 3584. The fit tabs 3596also provide rigidity to the anti-retraction mechanism 3590.Accordingly, when the plunger member 3516 is pulled proximally, thebrake tabs 3592 (because of their elasticity and angle) exert an outwardforce on the anti-retraction mechanism 3590. This outward force istransferred through the anti-retraction mechanism 3590 and the fit tabs3596 to push against the inside of the second recess 3584 of the fingerflange 3500 due to the rigidity of the anti-retraction mechanism 3590.This outward force is the reactive force to the frictional and reactionforces applied to the plunger member 3516 to prevent its proximalmovement.

FIGS. 54 to 56 depict a dual chamber injection system 4000 with a fingerflange 4080 having an anti-retraction feature 4090 according to someembodiments. The dual chamber injection system 4000 has many of the samecomponents as the dual chamber injection system 3500 depicted in FIGS.49 to 53 and described above. Those components have the same referencenumerals as the corresponding components in the dual chamber injectionsystem 3500. The difference between the dual chamber injection systems3500, 4000 is in the finger flanges 3590, 4090. Unlike the finger flange3590 depicted in FIGS. 50 and 51 , which has a “C” shaped opening 3586for receiving the plunger member 3516, the finger flange 4090 depictedin FIGS. 55 and 56 has an “O” shaped opening 4086 for receiving theplunger member 3516. The “O” shaped opening 4086 provides an additionalmechanism for preventing removal of the plunger member 3516 from thedual chamber injection system 4000 after use.

As shown in FIG. 56 , the anti-retraction mechanism 4090 in the fingerflange 4080 has an “O” and/or rectangular shape. The anti-retractionmechanism 4090 can be cut from a sheet of metal. Due to the “O” and/orrectangular shape of the finger flange 4080, the finger flange 4080 issnapped onto the small flange 3511 from a proximal direction duringassembly. Then the plunger member 3516 is inserted through an “O” shapedopening 4086 in the finger flange 4080. The “O” shaped opening 4086 inthe finger flange 4080 also aligns the plunger member 3516 in thesyringe body 3510.

The brake tabs 4092 in the anti-retraction mechanism 4090 depicted inFIG. 56 are identical to the brake tabs 3592 in the anti-retractionmechanism 3590 depicted in FIG. 51 , which are described above. Theretention tab 4094 in the anti-retraction mechanism 4090 depicted inFIG. 56 are similar to the retention tabs 3594 in the anti-retractionmechanism 3590 depicted in FIG. 51 , which are described above. Thedifference is that there is a single retention tab 4094 inanti-retraction mechanism 4090, while there is a pair of retention tabs3594 in anti-retraction mechanism 3590. The fit tabs 4096 in theanti-retraction mechanism 4090 depicted in FIG. 56 are similar to thefit tabs 3596 in the anti- retraction mechanism 3590 depicted in FIG. 51, which are described above. The difference is that there are three fittabs 4096 in anti-retraction mechanism 4090, while there are four fittabs 3594 in anti-retraction mechanism 3590.

The anti-retraction mechanism 4090 depicted in FIGS. 54 to 56 issymmetrical, simplifying high volume assembly whether manual orautomated. In embodiments where the plunger member (not shown) hasannular grooves and/or threads, the anti-retraction mechanism 4090 mayprevent removal of plunger member 3516 from the dual chamber injectionsystem 4000. Further, the pair of long beams in the “O” shapedanti-retraction mechanism 4090 are deformable, allowing theanti-retraction mechanism 4092 bow outward, thereby transferring anoutside reactive force to the interior walls of the second recess 4084via the outside/long fit tabs 4096.

While the prefilled dual chamber safety injection systems depicted anddescribed herein include syringes with staked needles, the injectionconfigurations and detent dual chamber configurations described hereincan be used with cartridges an auto injector, and injection systems withLuer connectors, transfer pipes, and no needles such as those describedin U.S. Utility patent application Ser. Nos. 15/801,281 and 15/801,259,which were previously incorporated by reference herein.

Various exemplary embodiments of the invention are described herein.Reference is made to these examples in a non-limiting sense. They areprovided to illustrate more broadly applicable aspects of the invention.Various changes may be made to the invention described and equivalentsmay be substituted without departing from the true spirit and scope ofthe invention. In addition, many modifications may be made to adapt aparticular situation, material, composition of matter, process, processact(s) or step(s) to the objective(s), spirit or scope of the presentinvention. Further, as will be appreciated by those with skill in theart that each of the individual variations described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentinventions. All such modifications are intended to be within the scopeof claims associated with this disclosure.

Any of the devices described for carrying out the subject diagnostic orinterventional procedures may be provided in packaged combination foruse in executing such interventions. These supply “kits” may furtherinclude instructions for use and be packaged in sterile trays orcontainers as commonly employed for such purposes.

The invention includes methods that may be performed using the subjectdevices. The methods may comprise the act of providing such a suitabledevice. Such provision may be performed by the end user. In other words,the “providing” act merely requires the end user obtain, access,approach, position, set-up, activate, power-up or otherwise act toprovide the requisite device in the subject method. Methods recitedherein may be carried out in any order of the recited events which islogically possible, as well as in the recited order of events.

Exemplary aspects of the invention, together with details regardingmaterial selection and manufacture have been set forth above. As forother details of the present invention, these may be appreciated inconnection with the above-referenced patents and publications as well asgenerally known or appreciated by those with skill in the art. Forexample, one with skill in the art will appreciate that one or morelubricious coatings (e.g., hydrophilic polymers such aspolyvinylpyrrolidone-based compositions, fluoropolymers such astetrafluoroethylene, PTFE, hydrophilic gel or silicones) may be used inconnection with various portions of the devices, such as relativelylarge interfacial surfaces of movably coupled parts, if desired, forexample, to facilitate low friction manipulation or advancement of suchobjects relative to other portions of the instrumentation or nearbytissue structures. The same may hold true with respect to method-basedaspects of the invention in terms of additional acts as commonly orlogically employed.

In addition, though the invention has been described in reference toseveral examples optionally incorporating various features, theinvention is not to be limited to that which is described or indicatedas contemplated with respect to each variation of the invention. Variouschanges may be made to the invention described and equivalents (whetherrecited herein or not included for the sake of some brevity) may besubstituted without departing from the true spirit and scope of theinvention. In addition, where a range of values is provided, it isunderstood that every intervening value, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention.

Also, it is contemplated that any optional feature of the inventivevariations described may be set forth and claimed independently, or incombination with any one or more of the features described herein.Reference to a singular item, includes the possibility that there areplural of the same items present. More specifically, as used herein andin claims associated hereto, the singular forms “a,” “an,” “said,” and“the” include plural referents unless the specifically stated otherwise.In other words, use of the articles allow for “at least one” of thesubject item in the description above as well as claims associated withthis disclosure. It is further noted that such claims may be drafted toexclude any optional element. As such, this statement is intended toserve as antecedent basis for use of such exclusive terminology as“solely,” “only” and the like in connection with the recitation of claimelements, or use of a “negative” limitation.

Without the use of such exclusive terminology, the term “comprising” inclaims associated with this disclosure shall allow for the inclusion ofany additional element--irrespective of whether a given number ofelements are enumerated in such claims, or the addition of a featurecould be regarded as transforming the nature of an element set forth insuch claims. Except as specifically defined herein, all technical andscientific terms used herein are to be given as broad a commonlyunderstood meaning as possible while maintaining claim validity.

The breadth of the present invention is not to be limited to theexamples provided and/or the subject specification, but rather only bythe scope of claim language associated with this disclosure.

What is claimed is:
 1. An injection system, comprising: a syringe bodydefining a proximal opening at a proximal end thereof and a distalneedle interface at a distal end thereof; proximal and distal stoppermembers disposed in the syringe body, forming a proximal drug chamberbetween the proximal and distal stopper members and a distal drugchamber between the distal stopper member and the distal end of thesyringe body; a plunger member configured to be manually manipulated toinsert the proximal stopper member relative to the syringe body, whereinthe plunger member has a smooth exterior surface; a fluid conveyingassembly; and a finger flange comprising an anti-retraction mechanism,the anti-retraction mechanism having a brake tab configured to providean opposing force to the plunger member to prevent proximal movementthereof relative to the brake tab, and a retention feature configured tomaintain the anti-retraction mechanism in a recess in the finger flange.2. The system of claim 1, wherein the finger flange further comprisesanother recess configured to mount the finger flange on a flange of thesyringe body.
 3. The system of claim 1, wherein the anti-retractionmechanism further comprises a plurality of fit tabs configured to reducea tolerance between the recess and a dimension of the anti-retractionmechanism.
 4. The system of claim 1, wherein the anti-retractionmechanism is a metal clip.
 5. The system of claim 1, wherein the braketab is an elastic and self-energizing pawl.
 6. The system of claim 5,wherein the brake tab is disposed at an acute angle in a distaldirection relative to a plane of the anti-retraction mechanism.
 7. Thesystem of claim 6, wherein the acute angle and an elasticity of thebrake tab increases a frictional force against the plunger member uponretraction in a proximal direction.
 8. The system of claim 6, whereinthe acute angle and an elasticity of the brake tab cause the brake tabto exerts an outward force through the anti-retraction mechanism to aninner wall of the finger flange when the plunger member is retracted ina proximal direction.
 9. The system of claim 1, wherein the fingerflange further comprises an opening having an edge configured tointerfere with and retain the anti-retraction mechanism in the recess.10. The system of claim 1, wherein the anti-retraction mechanism has a“C” shape.
 11. The system of claim 1, wherein the anti-retractionmechanism has an “O” shape.
 12. The system of claim 1, wherein theanti-retraction mechanism prevents removal of the plunger member fromthe syringe body after the plunger member has been inserted into thesyringe body.
 13. The system of claim 1, wherein the opposing forcecomprises a frictional force and a reaction force.
 14. The system ofclaim 1, wherein the brake tab is configured to penetrate the smoothexterior surface of plunger member when the plunger member movesproximally relative to anti-retraction mechanism.
 15. A multiple chambersafe injection system, comprising: a syringe body defining a syringebody interior and a distal coupling member at a distal end thereof;proximal and distal stopper members disposed in the syringe bodyinterior, forming a proximal chamber between the proximal and distalstopper members and a distal chamber between the distal stopper memberand the distal end of the syringe body; a plunger member configured tobe manually manipulated to insert the proximal stopper member relativeto the syringe body; a mix tube disposed in the syringe body interior;and a vent plug disposed at least partially in the distal couplingmember and defining a plurality of channels configured to allow a gas toexit the syringe body interior while forming a liquid tight seal.
 16. Anautoinjector system, comprising: a disposable injection systemcomprising an injection system body having proximal and distal ends, andan injection system body interior therebetween, a stopper memberdisposed in the injection system body interior, a plunger member coupledto the stopper member, a finger flange coupled to the injection systembody at the proximal end thereof, a needle hub assembly coupled to theinjection system body at the distal end thereof, and a rigid needleshield coupled to the needle hub assembly; and a reusable drive system,comprising a drive system body having a drive system body interior, aplunger actuator/pusher to move the plunger member distally relative tothe injection system body when the injection system is mounted in thedrive system, and a flange holder/carriage to move the injection systemdistally or proximally relative to the drive system body when theinjection system is mounted in the drive system.
 17. The system of claim16, the drive system further comprising: a first motor to move theplunger actuator/pusher; a second motor to move the flangeholder/carriage; a controller operatively coupled to the first andsecond motors; a display operatively coupled to the controller; and asensor operative coupled to the controller.
 18. The system of claim 17,wherein the sensor is selected from the group consisting of anaccelerometer, a contact sensor, a position sensor, a gyroscope, athermometer, and a skin contact sensor.
 19. The system of claim 17,wherein the drive system comprises a plurality of sensors.